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[0] Allman JM, Hakeem A, Erwin JM, Nimchinsky E, Hof P, The anterior cingulate cortex. The evolution of an interface between emotion and cognition.Ann N Y Acad Sci 935no Issue 107-17 (2001 May)

[0] Schicknick H, Schott BH, Budinger E, Smalla KH, Riedel A, Seidenbecher CI, Scheich H, Gundelfinger ED, Tischmeyer W, Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR.Cereb Cortex 18:11, 2646-58 (2008 Nov)

[0] Kakade S, Dayan P, Dopamine: generalization and bonuses.Neural Netw 15:4-6, 549-59 (2002 Jun-Jul)

[0] Pawlak V, Kerr JN, Dopamine receptor activation is required for corticostriatal spike-timing-dependent plasticity.J Neurosci 28:10, 2435-46 (2008 Mar 5)

[0] Daw ND, Doya K, The computational neurobiology of learning and reward.Curr Opin Neurobiol 16:2, 199-204 (2006 Apr)

[0] Schultz W, Multiple reward signals in the brain.Nat Rev Neurosci 1:3, 199-207 (2000 Dec)[1] Schultz W, Tremblay L, Hollerman JR, Reward processing in primate orbitofrontal cortex and basal ganglia.Cereb Cortex 10:3, 272-84 (2000 Mar)

[0] Schultz W, Tremblay L, Hollerman JR, Reward processing in primate orbitofrontal cortex and basal ganglia.Cereb Cortex 10:3, 272-84 (2000 Mar)

[0] Dzirasa K, Ribeiro S, Costa R, Santos LM, Lin SC, Grosmark A, Sotnikova TD, Gainetdinov RR, Caron MG, Nicolelis MA, Dopaminergic control of sleep-wake states.J Neurosci 26:41, 10577-89 (2006 Oct 11)

[0] Hikosaka O, Nakamura K, Sakai K, Nakahara H, Central mechanisms of motor skill learning.Curr Opin Neurobiol 12:2, 217-22 (2002 Apr)

[0] Lavin A, Nogueira L, Lapish CC, Wightman RM, Phillips PE, Seamans JK, Mesocortical dopamine neurons operate in distinct temporal domains using multimodal signaling.J Neurosci 25:20, 5013-23 (2005 May 18)[1] Pirot S, Godbout R, Mantz J, Tassin JP, Glowinski J, Thierry AM, Inhibitory effects of ventral tegmental area stimulation on the activity of prefrontal cortical neurons: evidence for the involvement of both dopaminergic and GABAergic components.Neuroscience 49:4, 857-65 (1992 Aug)

[0] Kilgard MP, Merzenich MM, Cortical map reorganization enabled by nucleus basalis activity.Science 279:5357, 1714-8 (1998 Mar 13)

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ref: -2014 tags: dopamine medium spiny neurons calcium STDP PKA date: 01-07-2020 03:43 gmt revision:2 [1] [0] [head]

PMID-25258080 A critical time window for dopamine actions on the structural plasticity of dendritic spines

  • Remarkably short time window for dopamine to modulate / modify (aggressive) STDP protocol.
  • Showed with the low-affinity calcium indicator Fluo4-FF that peak calcium concentrations in spines is not affected by optogenetic stimulation of dopamine fibers.
  • However, CaMKII activity is modulated by DA activity -- when glutamate uncaging and depolarization was followed by optogenetic stimulation of DA fibers followed, the FRET sensor Camui-CR reported significant increases of CaMKII activity.
  • This increase was abolished by the application of DRAPP-32 inhibiting peptide, which blocks the interaction of dopamine and cAMP-regulated phospoprotein - 32kDa (DRAPP-32) with protein phosphatase 1 (PP-1)
    • Spine enlargement was induced in the absence of optogenetic dopamine when PP-1 was inhibited by calculin A...
    • Hence, phosphorylation of DRAPP-32 by PKA inhibits PP-1 and disinihibts CaMKII. (This causal inference seems loopy; they reference a hippocampal paper, [18])
  • To further test this, they used a FRET probe of PKA activity, AKAR2-CR. This sensor showed that PKA activity extends throughout the dendrite, not just the stimulated spine, and can respond to DA release directly.

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ref: -0 tags: dLight1 dopamine imaging Tian date: 12-05-2019 17:27 gmt revision:0 [head]

PMID-29853555 Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

  • cpGFP based sensor. ΔF/F~3\Delta F / F ~ 3 .

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ref: -0 tags: STDP dopamine hippocampus date: 01-16-2019 21:56 gmt revision:1 [0] [head]

PMID-26516682 Retroactive modulation of spike timing-dependent plasticity by dopamine.

  • Here we show that dopamine, a positive reinforcement signal, can retroactively convert hippocampal timing-dependent synaptic depression into potentiation.
  • This effect requires functional NMDA receptors and is mediated in part through the activation of the cAMP/PKA cascade.
  • Mouse horizontal slices.
  • Plasticity induced by 100 pairings of a single EPSP followed by a postsynaptic spike (heavy-handed?)
  • Pre-before-post @ 10ms -> LTP
  • Post-before-pre @ -20ms -> LTD
  • Post-before-pre @ -10ms -> LTP (?!)
    • Addition of Dopamine antagonist (D2: sulpiride, D1/D5: SCH23390) prevented LTP and resulted in LTD.
  • Post-before-pre @ -20ms -> LTP in the presence of 20 uM DA.
    • The presence of DA during coordinated spiking activity widense the timing interval for induction of LTP.
  • What about if it's applied afterward?
  • 20 uM DA applied 1 minute (for 10-12 minutes) after LTD induction @ -20 mS converted LTD into LTP.
    • This was corrected by addition of the DA agonists.
    • Did not work if DA was applied 10 or 30 minutes after the LTD induction.
  • Others have shown that this requires functional NMDA receptors.
    • Application of NMDA agonist D-AP5 after post-before-pre -20ms did not affect LTD.
    • Application of D-AP5 before DA partially blocked conversion of LTD to LTP.
    • Application of D-AP5 alone before induction did not affect LTD.
  • This is dependent on the cAMP/PKA signaling cascade:
    • Application of forskolin (andenylyl cyclase AC activator) converts LTD -> LTP.
    • Dependent on NMDA.
  • PKA inhibitor H-89 alsoblocked LTD -> P.

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ref: -0 tags: concentation of monoamine dopamine serotonin and norepinephrine in the brain date: 04-28-2016 19:38 gmt revision:3 [2] [1] [0] [head]

What are the concentrations of the monoamines in the brain? (Purpose: estimate the required electrochemical sensing area & efficiency)

  • Dopamine: 100 uM - 1 mM local, extracellular.
    • PMID-17709119 The Yin and Yang of dopamine release: a new perspective.
  • Serotonin (5-HT): 100 ng/g, 0.5 uM, whole brain (not extracellular!).
  • Norepinephrine / noradrenaline: 400 nm/g, 2.4 uM, again whole brain.
    • PMID-11744005 An enriched environment increases noradrenaline concentration in the mouse brain.
    • Also has whole-brain extracts for DA and 5HT, roughly:
      • 1200 ng/g DA
      • 400 ng/g NE
      • 350 ng/g 5-HT
  • So, one could imagine ~100 uM transient concentrations for all 3 monoamines.

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ref: bookmark-0 tags: basal ganglia dopamine reinforcement learning Graybeil date: 03-06-2012 18:14 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16271465 The basal ganglia: learning new tricks and loving it

  • BG analogous to the anterior forebrain pathway (AFP), which is necessary for song learning in young birds. Requires lots of practice and feedback. Studies suggest e.g. that neural activity in the AFP is correlated with song variability, and that the AFP can adjust ongoing activity in effector motor pathways.
    • LMAN = presumed homolog of cortex that receives basal ganglia outflow. Blockade of outflow from LMAN to RA creates stereotyped singing.
  • To see accurately what is happening, it's necessary to record simultaneously, or in close temporal contiguity, striatal and cortical neurons during learning.
    • Pasupathy and biller showed that changes occur in the striatum than cortex during learning.
  • She cites lots of papers -- there has been a good bit of work on this, and the theories are coming together. I should be careful not to dismiss or negatively weight things.
  • Person and Perkel [48] reports that in songbirds, the analogous GPi to thalamus pathway induces IPSPs as well as rebound spikes with highly selective timing.
  • Reference Levenesque and Parent PMID-16087877 who find elaborate column-like arrays of striatonigral terminations in the SNr, not in the dopamine-containing SNpc.

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ref: Costa-2006.1 tags: Rui Costa Miguel Nicolelis Dopamine depletion excess cortex striatum hyperkinesia akinesia parkinsons DAT-KO date: 03-02-2012 01:03 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-17046697 Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction.

  • used rats where they could rapidly switch between dopamine depletion (0.2%) and overexpression (500%)
  • most cortical and striatal neurons ( approximately 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia,
    • buuut the overall cortical firing rate remained unchanged
  • repeated dopamine depletion is accompanied by the loss of glutamergic synapses in striatopallidal neurons (Day et al 2006) PMID-16415865 (Kaneda et al 2005). PMID-16367790
  • with Marc Caron
  • Dopamine is believed to modulate positively the direct striatal pathway that contains predominantly D1-type receptors and disinhibits cortical neurons to modulate negatively the indirect pathway that predominantly contains D2-type receptors and increased crotical inhibition (Albin et al 1989 {1050}, Filion and Tremblay 1991; Gerfen 1992, Parr-Brownlie and Hyland, 2005).
  • According to the classical view (Albin et al 1989), lack of DA release should lead to inhibition of cortical activity and an inability to produce movement, while an excess of Dopamine should lead to increased cortical activity and hyperactivity (Gerfen, 1992).
    • mouse model: DDD PMID-17030735[] (dopamine transporter knockout)

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ref: -0 tags: Albin basal ganglia dopamine 1989 parkinsons huntingtons hemiballismus date: 03-02-2012 00:28 gmt revision:1 [0] [head]

PMID-2479133 The functional anatomy of basal ganglia disorders.

  • Matrix neurons mainly containing substance P mainly project upon the GPi or SNr
    • while those containing enkephalins project on the GPe.
  • Striosome neurons projecting to the SNc contain mainly substance P.
  • Classical hypothesis:
  • Hyperkinetic disorders, which are characterized by an excess of abnormal movements, are postulated to result from the selective impairment of striatal neurons projecting to the lateral globus pallidus.
    • These are suppressed by D2 receptor antagonists & exacerbated by dopamine agonists.
    • Chorea is a primary example.
    • Despite Huntingtons, traumatic, ischemic, or ablative lesions of the striatum in man or animals rarely produces chorea or atheosis (writhing movements).
    • In HD, cholinergic agonists will alleviate choreoatheosis, while anti-cholinergic drugs exacerbate it.
  • Hypokinetic disorders, such as Parkinson's disease, are hypothesized to result from a complex series of changes in the activity of striatal projection neuron subpopulations resulting in an increase in basal ganglia output.
    • opposite of HD, exacerbated by D2 antagonists and ameliorated by DA agonists, as well as anti-cholinergics.
  • Dystonia = the spontaneous assumption of unusual fixed postures lasting from seconds to minutes.

  • Standard model suggests that striatal lesions should result in spontaneous movements, while this is not the case in man or other mammals. (less inhibition on GPi / SNr -> greater susceptibility of the thalamus to competing programs (?))
  • hyperkinetic movements can be produced by infusing bicululline, a GABA receptor antagonist, into GPe -- silencing it.
  • In early HD, when chorea is most prominent, there is a selective loss of striatal neurons projecting to the LGP (enkephalin staining).
    • Substance P containing neurons are lost later in the disease.
  • Administration of D2 antagonists increases the synthesis of enkephalins and pre-proenkephalin mRNA in the striatum.
    • This presumably represents increases in neuronal activity.
    • Inhibition of GPe neurons decreases hyperkinetic movements? But STN is excitatory? This does not add up.
  • Hemiballismus may be caused by disinhibition of SNr (?) and the VA/VL/MD/CM-Pf thalamocortical projections.

Saccades:

  • In both PD and HD, there are both increases in the latency of initiation of saccades, slowing of saccadic velocity, and interruption of saccades.
    • In HD, there is an early loss of substance-P containing striatal terminals in the SNr, possibly resulting in over-inhibition of tectal neurons.
    • HD patients cannot supress saccades to flashed stimulus.
    • No abnormalities in saccadic control in tourette's syndrome.
  • Hikosaka: suggest that caudate neurons involved in the initiation of saccades are part of a mechanism in which sensory data are evaluated in the context of learned behaviors and anticipated actions, and then used to initiate behavior.

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ref: -0 tags: dopamine reinforcement learning funneling reduction basal ganglia striatum DBS date: 02-28-2012 01:29 gmt revision:2 [1] [0] [head]

PMID-15242667 Anatomical funneling, sparse connectivity and redundancy reduction in the neural networks of the basal ganglia

  • Major attributes of the BG:
    • Numerical reduction in the number of neurons across layers of the 'feed forward' (wrong!) network,
    • lateral inhibitory connections within the layers
    • modulatory effects of dopamine and acetylcholine.
  • Stochastic decision making task in monkeys.
  • Dopamine and ACh deliver different messages. DA much more specific.
  • Output nuclei of BG show uncorrelated activity.
    • THey see this as a means of compression -- more likely it is a training signal.
  • Striatum:
    • each striatal projection neuron receives 5300 cortico-striatal synapses; the dendritic fields of same contains 4e5 axons.
    • Say that a typical striatal neuron is spherical (?).
    • Striatal dendritic tree is very dense, whereas pallidal dendritic tree is sparse, with 4 main and 13 tips.
    • A striatal axon provides 240 synapses in the pallidum and makes 10 contacts with one pallidal neuron on average.
  • I don't necessarily disagree with the information-compression hypothesis, but I don't disagree either.
    • Learning seems a more likely hypothesis; could be that we fail to see many effects due to the transient nature of the signals, but I cannot do a thorough literature search on this.

PMID-15233923 Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons.

  • Same task as above.
  • both ACh (putatively, TANs in this study) and DA neurons respond to reward related events.
  • dopamine neurons' response reflects mismatch between expectation and outcome in the positive domain
  • TANs are invariant to reward predictability.
  • TANs are synchronized; most DA neurons are not.
  • Striatum displays the densest staining in the CNS for dopamine (Lavoie et al 1989) and ACh (Holt et al 1997)
    • Depression of striatal acetylcholine can be used to treat PD (Pisani et al 2003).
    • Might be a DA/ ACh balance problem (Barbeau 1962).
  • Deficit of either DA or ACh has been shown to disrupt reward-related learning processes. (Kitabatake et al 2003, Matsumoto 1999, Knowlton et al 1996).
  • Upon reward, dopaminergic neurons increase firing rate, whereas ACh neurons pause.
  • Primates show overshoot -- for a probabalistic relative reward, they saturate anything above 0.8 probability to 1. Rats and pigeons do not show this effect (figure 2 F).

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ref: -0 tags: DBS dopamine synaptic plasticity striatum date: 02-27-2012 21:57 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-11285003 Dopaminergic control of synaptic plasticity in the dorsal striatum.

  • Repetitive stimulation of corticostriatal fibers causes a massive release of glutamate and DA in the striatum, and depending on the glutamate receptor subtype preferentially activated, produces either long-term depression (LTD) or long-term potentiation (LTP) of excitatory synaptic transmission.
  • D1 and D2 (like) receptors interact synergistically to allow LTD formation, and in opposition while inducing LTP.
  • Stimulation of DA receptors has been shown to modulate voltage-dependent conductances in striatal spiny neurons, but it does not cause depolarization or hyperpolarization (Calabresi et al 2000a PMID-11052221; Nicola et al 2000)
  • Striatal spiny neurons present a high degree of colocalization of subtypes of DA and glutamate receptors. PMID-9215599
  • Striatal cells have up and down states. Wilson and Kawaguchi 1996 PMID-8601819
  • Both LTD and LTP are induced in the striatum by the repetitive stimulation of corticostriatal fibers.
    • Repetition is associated with the dramatic increase of both glutamate and DA in the striatum. (presynaptic?)
  • LTP is enhanced by blocking or removing D2 receptors.
  • More complexity here - in terms of receptors and blocking. (sure magnesium blocks NMDA receptors, but there are many other drugs used...)

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ref: -0 tags: dopamine reward prediction striatum error striatum orbitofrontal reward date: 02-24-2012 21:26 gmt revision:1 [0] [head]

PMID-11105648 Involvement of basal ganglia and orbitofrontal cortex in goal-directed behavior.

  • Many regions have a complex set of activations, but dopamine neurons appear more homogenous: they report the error in reward prediction.
    • "The homogeneity of responsiveness across the population of dopamine neurons indicates that this error signal is widely broadcast to dopamine terminal regions where it could provide a teaching signal for synaptic modifications underlying the learning of goal-directed appetitive behaviors."
    • Signals are not contingent on the type of behavior needed to obtain the reward, and hence represent a relatively 'pure' reward prediction error.
  • Unlike dopamine neurons, many striatal neurons respond to predicted rewards, although at least some may reflect the relative degree of predictability in the magnitude of the responses to reward.
  • Neuronal activations in the orbitofrontal cortex appear to involve less integration of behavioral and reward-related information, but rather incorporate another aspect of reward, the relative motivational significance of different rewards.
  • Processing is hierarchical (or supposed to be so):
    • Dopamine neurons provide a relatively pure signal of an error in reward prediction,
    • Striatal neurons signal not only reward, but also behavioral contingencies,
    • Orbitofrontal neurons signal reward and incorporate relative reward preference.

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ref: Salin-2002.06 tags: STN HFS DBS stimulation dopamine date: 02-22-2012 18:23 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-12077209[0][] High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat.

  • they wanted to measure the cellular/molecular effects of STN DBS - reasonable.
    • in-situ hybridization histochemistry and immunocytochemnistry.
  • HFS of the STN decreases the metabolic activity of STN neurons (cytochrome oxidase (CoI) levels decreased!),
    • However it did not affect the overexpression of enkephalin {1135} mRNA or the decrease in substance P in the ipsilateral striatum.
    • Decreased/corrects glutamate decarboxylase 67 (GAD67) in the substantia nigra following STN lesion, worsened in the entopeduncular (GPe-ish: see wiki) nucleus, no change in GPi.
    • HFS, however, increases c-fos activity, which seems to be involved in immediate early gene induction and stress response (as well as 8,000 other papers about this protein)
  • this stimulation may not simply cause interruption of STN outflow.
  • STN on the order of 300ua through a 200um teflon-coated stainless bipolar (twisted pair) electrode (important to consider)
  • unilateral HFS in STN in hemiparkinsonian rats can induce dyskinesias
    • buuut a higher intensity of stimulation was required to elicit dyskinesia in animals with the dopamine lesion as compared to the intact rats. Parkinsonian animals are more resistant to HFS of the STN.
    • Therefore they matched the stimulus intensity to the behavior correlates, not the absolute values of the currents.
  • STN HFS in animals with dopamine lesions on the same brain side may prevent the previously reported dopamine hyperactivity in the contralateral hemisphere.
  • note bene, the entopeduncular nucleus is probably not a good taget for surgical treatment PMID-14602091[1][] High frequency stimulation of the entopeduncular nucleus has no effect on striatal dopaminergic transmission.

____References____

[0] Salin P, Manrique C, Forni C, Kerkerian-Le Goff L, High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat.J Neurosci 22:12, 5137-48 (2002 Jun 15)
[1] Meissner W, Harnack D, Hoessle N, Bezard E, Winter C, Morgenstern R, Kupsch A, High frequency stimulation of the entopeduncular nucleus has no effect on striatal dopaminergic transmission.Neurochem Int 44:4, 281-6 (2004 Mar)

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ref: -0 tags: enkephalin DBS dopamine regulation date: 02-22-2012 18:22 gmt revision:0 [head]

PMID-9835393 Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior.

  • I can't be more terse or informative than the abstract, so I reprint it here:
  • Neurons of the direct pathway express the peptide dynorphin and the D1 dopamine receptor,
  • whereas indirect pathway neurons express the peptide enkephalin and the D2 receptor.
  • we used D1- or D2-receptor-mediated induction of immediate-early genes as a cellular response [reporter] in direct or indirect projection neurons, respectively, to investigate the role of these opioid peptides.
  • Our results suggest that the specific function of dynorphin and enkephalin is to dampen excessive activation of these neurons by dopamine and other neurotransmitters.
  • Levels of these opioid peptides are elevated by repeated, excessive activation of these pathways, which appears to be an adaptive or compensatory response.
  • Behavioral consequences of increased opioid peptide function in striatal output pathways may include behavioral sensitization (dynorphin) and recovery of motor function (enkephalin).

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ref: RodriguezOroz-2011.01 tags: DBS dopamine impulse control spain pamplona ventral beta date: 02-22-2012 17:02 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-21059746[0] Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson’s disease

  • recorded LFP in the STN of 28 patients.
    • of these 10 had impulse control disorders, 9 had dyskinesias, and 9 had no complications.
  • compared ON and OFF medication.
  • no difference between groups in off states.
  • large differences in ON states.
    • Impulse control problems: theta-alpha activity(4-10 Hz) 6 Hz mean.
      • Larger coherence with frontal regions 4-7.5 Hz.
    • Dyskinesias: higher frequency theta-alpha 8 Hz mean.
      • Higher coherence with motor areas, 7.5 - 10Hz.
    • No problems: no noticeable LFP oscillations (?).
  • PD patients often have side-effects of Punding and hobbyism.
    • Does meth treat PD? Selegiline does. Fascinating history there regarding combining MAOI + amphetamine --> effective PD drug.
    • Why does both meth and levodopa induce impulsivity?
    • Some of the other effects of L-DOPA treatment: hypersexuality, manic behavior or shopping.
    • Lesion of the subthalamic nucleus by infarction or tumor is associated with behavioral alterations including agitation, manic states and logorrhoea, with or without hemiballismus.
  • In some patients with ICD (impulse control disorders) induced by subthalamic nucleus deep brain stimulation, the abnormal behavior was provoked by stimulation with a ventral contact and suppressed by switching it off. (dorsal region is more motor).
    • In three patients with ICD, stimulation through the ventral contact induced a euphoric state -- PPN?
  • STN recordings from rats and monkeys modify their frequency in response to reward related tasks (Aron and Poldrack 2006); in humans the STN is active during an inhibition task (LI et al 2008).
  • LFP recordings from the treatment electrode were very low! 16uV.
  • Typical results show large differences between ON and OFF: ON show more activity > 60 Hz, OFF more < 60 Hz (Brown et al 2001; Brown 2003 Gatev et al 2006).
  • LFP recordings in PD patients from the STN showed that emotional stimulus led to a decrease in alpha power in the ventral contacts (Brucke et al 2007), whereas active movement led to a decrease in the beta power recorded in the dorsal subthalamic nucleus (Alegre et al 2005).
  • Original work on STN mediating impulsivity: Delong 1983 PMID-6422317 The neurophysiologic basis of abnormal movements in basal ganglia disorders.
    • Single cell studies in the basal ganglia of behaving animals have revealed specific relations of neuronal activity to movements of individual body parts and a relation to specific parameters of movement, particularly direction, amplitude, and velocity. (no fulltext available).

____References____

[0] Rodriguez-Oroz MC, López-Azcárate J, Garcia-Garcia D, Alegre M, Toledo J, Valencia M, Guridi J, Artieda J, Obeso JA, Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson's disease.Brain 134:Pt 1, 36-49 (2011 Jan)

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ref: Magill-2001.01 tags: dopamine STN globus_pallidus cortex parkinsons DBS 6OHDA date: 02-22-2012 15:31 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-11566503[0] Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus-globus pallidus network

  • Compared unit activity STN / GP and EEG in rats under urethane anesthesia in control and 6OHDA rats.
  • DA depletion:
    • increased FR of STN neurons.
    • caused oscillations in GP neurons.
  • dopamine depletion causes the STN-GP circuit to become more reactive to the influence of the activity of cortical inputs. also see PMID-10632612[1]
  • oscillatory activity in the STN-GP network in anaesthetised rats is phase-locked to rhythmic cortical activity and is abolished by transient cortical activation as well as cortical ablation.
    • 15-20% of the network still oscillated following cortex removal, suggesting that intrinsic properties pattern activity when dopamine levels are reduced.
  • cool figures - nice recordings, high SNR, clear oscillations in the firing and ECoG signal

____References____

[0] Magill PJ, Bolam JP, Bevan MD, Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus-globus pallidus network.Neuroscience 106:2, 313-30 (2001)
[1] Magill PJ, Bolam JP, Bevan MD, Relationship of activity in the subthalamic nucleus-globus pallidus network to cortical electroencephalogram.J Neurosci 20:2, 820-33 (2000 Jan 15)

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ref: BAdi-2009.09 tags: dopamine L-Dopa levodopa agonist young reward novelty punisment learning date: 01-24-2012 04:05 gmt revision:1 [0] [head]

PMID-19416950[0] Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients

  • dopamine agonist administration in young patients with Parkinson's disease resulted in increased novelty seeking, enhanced reward processing, and decreased punishment processing may shed light on the cognitive and personality bases of the impulse control disorders, which arise as side-effects of dopamine agonist therapy in some Parkinson's disease patients.

____References____

[0] Bódi N, Kéri S, Nagy H, Moustafa A, Myers CE, Daw N, Dibó G, Takáts A, Bereczki D, Gluck MA, Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients.Brain 132:Pt 9, 2385-95 (2009 Sep)

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ref: Brown-2001.12 tags: EMG ECoG motor control human coherence dopamine oscillations date: 01-19-2012 21:41 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-11765129[0] Cortical network resonance and motor activity in humans.

  • good review.
  • No coherence between ECoG and eMG below 12 Hz; frequency coherence around 18 Hz.
    • This seen only in high-resolution ECoG; lower resolution signals blurs the sharp peak.
  • Striking narrowband frequency of coherence.
  • ECoG - ECoG coherence not at same frequency as EMG-ECoG.
  • Marked task-dependence of these coherences, e.g. for wrist extension and flexion they observed similar EMG/ECoG coherences; for different tasks using the same muscles, different patterns of coherence.
  • Pyramidal cell discharge tends to be phase-locked to oscillations in the local field potential (Murthy and Fetz 1996)
    • All synchronization must ultimately be through spikes, as LFPs are not transmitted down the spinal cord.
  • Broadband coherence is pathological // they note it occurred during cortical myclonus (box 2)
  • Superficial chattering pyramidal cells (!!) firing bursts of frequency at 20 to 80 Hz, interconnected to produce spike doublets (Jefferys 1996).
  • Dopamine restores coherence between EMG and ECoG in a PD patient.

____References____

[0] Brown P, Marsden JF, Cortical network resonance and motor activity in humans.Neuroscientist 7:6, 518-27 (2001 Dec)

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ref: Schultz-1998.07 tags: dopamine reward reinforcement_learning review date: 12-07-2011 04:16 gmt revision:1 [0] [head]

PMID-9658025[0] Predictive reward signal of dopamine neurons.

  • hot article.
  • reasons why midbrain Da is involved in reward: lesions, receptor blocking, electrical self-stimulation, and drugs of abuse.
  • DA neurons show phasic response to both primary reward and reward-predicting stimul.
  • 'All responses to rewards and reward-predicting stimuli depend on event predictability.
  • Just think of the MFB work with the rats... and how powerful it is.
  • most deficits following dopamine-depleting lesions are not easily explained by a defective reward signal (e.g. parkinsons, huntingtons) -> implying that DA has two uses: the labeling of reward, that the tonic enabling of postsynaptic neurons.
    • I just anticipated this, which is good :)
    • It is still a mystery how the neurons in the midbrain determine to fire - the pathways between reward and behavior must be very carefully segregated, otherwise we would be able to self-simulate
      • the pure expectation part of it is bound play a part in this - if we know that a certain event will be rewarding, then the expectation will diminish DA release.
  • predictive eye movements amerliorate behavioral perfromance through advance focusing. (interesting)
  • predictions are used in industry:
    • Internal Model Control is used in industry to predict future system states before they actually occur. for example, the fly-by-wire technique in aviation makes decisions to do particular manuvers based on predictable forthcoming states of the plane. (Like a human)
  • if you learn a reaction/reflex based on a conditioned stimulus, the presentation of that stimulus sets the internal state to that motivated to achieve the primary reward. there is a transfer back in time, which, generally, is what neural systems are for.
  • animals avoid foods that fail to influence important plasma/brain parameters, for example foods lacking essential amino acids like histidine, threonine, or methionine. In the case of food, the appearance/structure would be used to predict the slower plasma effects, and hence influence motivation to eat it. (of course!)
  • midbrain groups:
    • A8 = dorsal to lateral substantia nigra
    • A9 = pars compacta of substantia nigra, SNc
    • A10 = VTA, media to substantia nigra.
  • The characteristic polyphasic, relatively long impulses discharged at low frequencies make dpamine neurons easily distinguishable from other midbrain neurons.

____References____

[0] Schultz W, Predictive reward signal of dopamine neurons.J Neurophysiol 80:1, 1-27 (1998 Jul)

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ref: Allman-2001.05 tags: anterior cingulate dopamine spindle neurons review date: 12-15-2008 04:13 gmt revision:1 [0] [head]

PMID-11411161[0] The anterior cingulate cortex. The evolution of an interface between emotion and cognition

  • The ACC receives one of the riches dopaminergic innervations of any cortical area.
  • The ACC contains morphologically distinct spindle cells, a recent advance in hominid evolution. (Appears that they are also present in monkeys, since people can perform experiments there too).
  • A large body of EEG data indicates that the anterior cingulate is the source of a 4- to 7-Hertz signal present when the subject is performing a task requiring focused concentration.24 The amplitude of this signal increases with task difficulty.25 When the subject is restless and anxious, the signal is reduced or eliminated; when the anxiety is relieved with drugs, the signal is restored.

____References____

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ref: Schicknick-2008.11 tags: dopamine plasticity auditory cortex date: 12-15-2008 04:13 gmt revision:1 [0] [head]

PMID-18321872[0] Dopaminergic Modulation of Auditory Cortex-Dependent Memory Consolidation through mTOR.

  • I will annotate this paper later, after winter break.

____References____

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ref: Kakade-2002.07 tags: dopamine reward reinforcement learning Kakade Dayan date: 12-09-2008 21:27 gmt revision:1 [0] [head]

PMID-12371511[0] Dopamine: generalization and bonuses

  • suggest that some anomalies of dopamine activity is related to generalization and novelty. In terms of novelty, dopamine may be shaping exploration.
  • review results that DA activity signal a global prediction error for summed future reward in conditioning tasks.
    • above, A = pre-training; B = post-training; C = catch trial.
    • this type of model is essentially TD(0); it does not involve 'eligibility traces', but still is capable of learning.
    • remind us that these cells have been found, but there are many other different types of responses of dopmamine cells.
  • storage of these predictions involves the basolateral nuclei of the amygdala and the orbitofrontal cortex. (but how do these structures learn their expectations ... ?)
  • dopamine release is associated with motor effects that are species specific, like approach behaviors, that can be irrelevant or detrimental to the delivery of reward.
  • bonuses, for the authors = fictitious quantities added to rewards or values to ensure appropriate exploration.
  • resolution of DA activity ~ 50ms.
  • Romo & Schultz have found that there are phasic increases in DA activity to both rewarded and non-rewarded events/stimuli - something that they explain as 'generalization'. But - maybe it is something else? like a startle / get ready to move response?
  • They suggest that it is a matter of intermediate states where the monkey is uncertain as to what to do / what will happen. hum, not sure about this.

____References____

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ref: Pawlak-2008.03 tags: dopamine striatum cortex STDP plasticity NMDAR date: 10-08-2008 17:24 gmt revision:1 [0] [head]

PMID-18322089[0] Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity

  • Single action potentials (APs) backpropagate into the higher-order dendrites of striatal spiny projection neurons during cortically driven "up" states (Kerr and Plenz, 2004)
    • note: many 'up' states in the striatum do not contain an AP.
  • Blocking dopamine D1/D5 receptors prevented both LTD and LTP induction.
  • first paragraph has a ton of references! They note that burst spiking in cortical and striatal projection neurons is infrequent - mostly, there are single spikes - and so STDP investigations are more applicable than high frequency stimulation LTP induction.
  • tested in vitro -- para-horizontal sections into the dorsolateral striatum of young rat brain, whole-cell current clamp, GABA_A currents blocked.
  • striatal projection neurons (SPNs) have a strange mode of AP generation - their membrane potential rises for 120ms after current injection, followed by a spike. They used this and infrared differential microscopy of morphology to locate the projection neurons.
  • stimulated using extracellular current to layer 5 of the cortex or nearby white matter. kept microstim current to a minimum.
  • paired this with AP generation in the SPNs at varying time delays, both at low frequency (0.1Hz)
  • there are a few cholinergic neurons in the striatum, apparently.
  • demonstrated STDP: "synaptic strength is maximally enhanced when cortically evoked EPSPs lead a spike by 10 ms, whereas synaptic strength is maximally depressed when EPSPs follow a spike by 30 ms"
  • also tried eliciting bursts in the SPN, but: "the timing of EPSPs with single APs is as efficient in inducing synaptic plasticity as the timing of EPSPs with AP bursts"
  • the STDP / LTP / LTD was NMDA-R dependent.
  • blocked D1/D5 with SCH-23390, and found that they could not induce LTP / LTD.
  • block of D2 receptor advanced the onset of LTP and delayed the onset of LTD, to a less dramatic degree than the D1/D5 block. Long-term LTP/LTD magnitude was not effected.
  • why did these guys get in J. Neuroscience where as this is in Science? because the Science article studied medium spiny neurons, with GFP labeling the D1/D2 receptors?

____References____

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ref: Daw-2006.04 tags: reinforcement learning reward dopamine striatum date: 10-07-2008 22:36 gmt revision:1 [0] [head]

PMID-16563737[0] The computational neurobiology of learning and reward

  • I'm sure I read this, but cannot find it in m8ta anymore.
  • short, concise review article.
  • review evidence for actor-critic architectures in the prefrontal cortex.
  • cool: "Perhaps most impressively, a trial-by-trial regression analysis of dopamine responses in a task with varying reward magnitudes showed that the response dependence on the magnitude history has the same form as that expected from TD learning". trial by trial is where it's at! article: Midbrain Dopamine Neurons Encode a Quantitative Reward Prediction Error Signal

____References____

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ref: Schultz-2000.12 tags: review reward dopamine VTA basal ganglia reinforcement learning date: 10-07-2008 22:35 gmt revision:1 [0] [head]

PMID-11257908[0] Multiple Reward Signals in the Brain

  • deals with regions in the brain in which reward-related activity has been found, and specifically what the activity looks like.
  • despite the 2000 date, the review feels somewhat dated?
  • similar to [1] except much sorter..

____References____

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ref: Schultz-2000.03 tags: review orbitofrontal cortex basal ganglia dopamine reward reinforcement learning striatum date: 10-07-2008 03:53 gmt revision:1 [0] [head]

PMID-10731222[0] Reward processing in primate orbitofrontal cortex and basal ganglia

  • Orbitofrontal neurons showed three principal forms of reward-related activity during the performance of delayed response tasks,
    • responses to reward-predicting instructions,
    • activations during the expectation period immediately preceding reward and
    • responses following reward
    • above, reward-predicting stimulus in a dopamine neuron. Left: the animal received a small quantity of apple juice at irregular intervals without performing in any behavioral task. Right: the animal performed in an operant lever-pressing task in which it released a touch-sensitive resting key and touched a small lever in reaction to an auditory trigger signal. The dopamine neuron lost its response to the primary reward and responded to the reward-predicting sound.
  • for the other figures, read the excellent paper!

____References____

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ref: Dzirasa-2006.1 tags: Kafui dopamine sleep REM state-diagram SCLin date: 10-05-2008 17:37 gmt revision:2 [1] [0] [head]

PMID-17035544[0] Dopaminergic control of sleep-wake states

____References____

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ref: Hikosaka-2002.04 tags: motor learning SMA basal ganglia M1 dopamine preSMA review date: 10-05-2008 02:06 gmt revision:1 [0] [head]

PMID-12015240[0] Central mechanisms of motor skill learning

  • review article.
  • neurons in the SMA become active at particular transitions in sequential movements; neurons in the pre-SMA maybe active specifically at certain rank orders in a sequence.
    • Many neurons in the preSMA were activated during learning of new sequences
  • motor skill learning is associated with coactivation of frontal and partietal cortices.
  • With practice, accuracy of performance was acquired earlier than speed of performance. interesting...
  • Striatum:
    • Reversible blockade of the anterior striatum (associative region) leads to deficits in learning new sequences
    • blockade of the posterior striatum (motor region) leads to disruptions in the execution of learned sequences
  • Cerebellum: In contrast, blockade of the dorsal part of the dentate nucleus (which is connected with M1) does not affect learning new sequences, but disrupts the performance of learned sequences. The conclude from this that long-term memories for motor skills ma be storerd in the cerebellum.
  • Doya proposed that learning in the basal ganglia and cerebellum maybe guided by error signals, as opposed to the cerebral cortex.

____References____

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ref: AnguianoRodrAguez-2007.02 tags: serotonin learning dopamine date: 03-12-2007 02:30 gmt revision:0 [head]

PMID-17126827 Striatal serotonin depletion facilitates rat egocentric learning via dopamine modulation. facilitates - they get better! (more awake than controls? inability to forget?)

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ref: Shapovalova-2006.1 tags: dopamine learning neocortex rats russians D2 date: 03-12-2007 01:58 gmt revision:0 [head]

PMID-17216714 Motor and cognitive functions of the neostriatum during bilateral blocking of its dopamine receptors

  • systemic application of D1 selective blockers reduced learning in rats
    • probably this effect is not neostriatal:
  • local application of the same blocker on the cortex did not markedly affect learning, though it did effect initiation errors
  • D2 antagonist (raclopride) locally applied to the striatum blocked learning.

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ref: Dzirasa-2006.1 tags: DAT-KO Kafui Nicolelis sleep wake dopamine tyrosine synthesis date: 03-12-2007 01:50 gmt revision:1 [0] [head]

PMID-17035544 Dopaminergic control of sleep-wake states.

  • dopmergic activity is high in REM sleep!! perhaps this is involved in learning?
  • they have a good description of the DAT-KO model, and why it is good for both exessive levels of synaptic dopamine as well as depressed/parkinsonian levels...
  • also at http://hardm.ath.cx:88/pdf/Kafui2006.pdf

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ref: Lavin-2005.05 tags: dopamine PFC VTA prefrontal_cortex ventral_tegmentum 2005 date: 02-05-2007 20:37 gmt revision:1 [0] [head]

PMID-15901782[0]Mesocortical Dopamine Neurons Operate in Distinct Temporal Domains Using Multimodal Signaling

  • good paper, decent review of relevant infos in the introduction.
  • they suggest that the mesocortical system transmits fast signals about reward/salience via corelease of glutamate, whereas dopamine provides a more long-term modulator of cortical processing dynamics.
  • the ventral tegmental area provides dopamine to the prefrontal cortex.
  • DA levels in the PFC can increase ~10x above baseline for 10's of minutes.
    • these responses occur to both to unexpectedly rewarding stimuli as well as to aversive stimuli.
  • brief VTA stimulation invokes a short, transient (~200ms) inhibition of PFC in vivo, and this inhibition is typically blocked by DA antagonists. from: PMID-1436485[1]
    • transient inhibition begins ~20ms after VTA stimulation, which is barely enough time for activation of ionotropic receptors, let alone metabotropic DA receptors.
  • MFB stimulation evoked increased DA levels and an elevation in firing of nearby striatal neurons that outlasted the period of stimulation by > 300s.
  • strangely, the excitatory glutamergic response in the PFC to VTA stimulation is blocked by lesion of the MFB.
  • in suppport of co-release, TH-positive neurons in rats and primates are co-reactive for glutamate.
    • DA neurons can form glutamate synapses in vitro.
  • check it out:
    • midbrain DA neurons respond by firing a ~200ms burst of spikes to primary rewards, conditioned, or secondary rewards, rewards that are not predicted, and novel or unexpected stimuli.
    • DA neurons are activated by rewarding events that are better than predicted, remain unaffected by events that are as good as predicted, and are depressed by events that are worse than predicted (yet they do not cite any refs for this... there are a bunch of refs in the prev sentence. ) see:
    • stress can also increase PFC DA

____References____

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ref: Walton-2005.02 tags: dopamine anterior cingulate mesocortical date: 02-05-2007 19:19 gmt revision:2 [1] [0] [head]

PMID-15727537 The mesocortical dopamine projection to anterior cingulate cortex plays no role in guiding effort-related decisions.

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ref: notes-0 tags: dopamine addiction mesolimbic date: 0-0-2007 0:0 revision:0 [head]

experiment: animals initially learn that a light always lights up after pressing a switch which causes the administration of opioids. in successive trials the animal is not rewarded for pressing the switch, however the light (sometimes?) lights up following lever depression - and the animals continue to press the lever in the abscence of reward -- the reward has been transferred to the conditioned stimulus? http://druglibrary.org/schaffer/heroin/ase/chap_4.htm

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ref: Kilgard-1998.03 tags: dopamine basal_forebrain nucleus_basalis cortical_plasticity date: 0-0-2007 0:0 revision:0 [head]

PMID-9497289[0] Cortical map reorganization enabled by nucleus basalis activity

  • idea, very cool: that stimulation in the nucleus basalis (partially acetylcholine-releasing center in the brain) of the rat, when paired with audio tone presentation, causes the auditory cortex to to reorganize so as to better represent the presented stimulus(stimuli). Note the rats were not tasked with anything, and were placed in a soundproofed box.
  • stimulation protocol: 200ms of 70-150ua current delivered to the NB through bipolar platinum stimulation electrodes. current was set at the threshold needed to desynchronize cortical EEG during slow-wave sleep.
    • how ever did they come up with this metric? EEG desynchronizaton?
____References____
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ref: bookmark-0 tags: STDP hebbian learning dopamine reward robot model ISO date: 0-0-2007 0:0 revision:0 [head]

http://www.berndporr.me.uk/iso3_sab/

  • idea: have a gating signal for the hebbian learning.
    • pure hebbian learning is unsable; it will lead to endless amplification.
  • method: use a bunch of resonators near sub-critically dampled.
  • application: a simple 2-d robot that learns to seek food. not super interesting, but still good.
  • Uses ISO learning - Isotropic sequence order learning.
  • somewhat related: runbot!

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ref: Barik-1996.1 tags: parkinsons dopamine cerebellum D3 essential tremor ET date: 0-0-2007 0:0 revision:0 [head]

  • PMID-8930390
    • There is a high concentration of dopamine in the 9 and 10 lobule of the cerebellum. quote: similar but weaker than the D3 response in the nucelus accumbens.
    • lobules 9 and 10 are involved in vestibular control of posture (?)
  • D3 is metabotropic inhibitory (sorta): molecular biology of the dopamine receptor subtypes
  • D3 is an autoreceptor; antagonism probably increases DA synaptic transmission.
    • Amisulpride is a D3 antagonist of the autoreceptor, and is used to treat the depressive elements at low doses(where it blocks autoreceptor) of schizophrenia at high doses (blocks postsynaptic recepor).
  • PMID-14622169 dopamine receptor expression is repressed in parkinsonian patients.
  • PMID-16809426 French patients with familial essential tremor are associated with polymorphisms in the D3 receptor gene.
    • a mutation which increases the affinity for dopamine causes an increase in the cAMP and MAPK response.
    • this mutation is harder to treat with parkinson's drugs - they suggest D3 antagonists for these patients of essential tremor.

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ref: Stefani-1995.09 tags: electrophysiology dopamine basal_ganglia motor learning date: 0-0-2007 0:0 revision:0 [head]

PMID-8539419 Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and new perspectives.

  • D1 is inhibitory (modulatory) on striatal neurons.
  • D1 cloned in 1990
  • D1 stimulates adenyl cyclase. (cAMP)
  • D1 activity shown to be necessary, but not sufficient, to generate long-term depression in striatal slices.
  • SKF 38393 was designed as a selective D1 receptor agonist; it has been available since the late 70's; it has nanomolar affinity for D1-R. SKF 38393 inhibits action potential discharge in striatal neurons as measued through response to intracellular current depolarizations.
  • striatal cells project to the substantia nigra.
  • alternate hypothesis: D1 activation on the striatonigral afferents to the ventral tegmental area (VTA) promotes GABA release.
    • recall that the VTA projects to the frontal/prefrontal cortex (PFC) via the mesocortical dopiminergic pathway. http://grad.uchc.edu/phdfaculty/antic.html There, DA synapese on spines of distal dendrites in juxtaposition with glutamergic synapses. this guy posits that these DA synapses are involved in the pathology of schizophrenia, and he uses optical techniques to measure the DA/Glu synapses.
    • VTA is just below the red nucleus in rats.
  • some people report that SKF 38393 potentiated depolarizing membrane responses to exogenous NMDA (agonist, excitotoxin).
  • they prefer the magnesium-dependent LTD pathway.
    • D1 receptor antagonist SCH 23390 prevented the generation of LTD in striatum. (Calabresi et al 1992).
    • in DA-depleted slices, LTD could be restored by the co-administration of D1 and D2 agonists.

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ref: neuro notes-0 tags: Dopamine receptor D1 D2 date: 0-0-2007 0:0 revision:0 [head]

http://www.cnsforum.com/imagebank/section/receptor_systems_Dopaminergic/default.aspx

  • the D1 receptor is coupled to stimulatory G-proteins, which cause cell depolarization. (pathway: stimulatory g-protein -> actibation of adenylate cyclase converts ATP -> cAMP -> PKC -> phosphorylation of sodium (and calcium?) channel.
  • the D2 receptor (family?) is coupled to inhibitory G-proteins, which decrease the activity of adenylate cyclase. this is a pretty vague picture.

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ref: Lewis-2000.12 tags: UP_DOWN VTA dopamine D1 prefrontal cortex PFC date: 0-0-2007 0:0 revision:0 [head]

PMID-11073866 Ventral Tegmental Area Afferents to the Prefrontal Cortex Maintain Membrane Potential ‘Up’ States in Pyramidal Neurons via D1 Dopamine Receptors

  • need i say more?

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ref: Di-1994.06 tags: dopamine NMDA striatum globus_pallidus ion_channels neurotransmitters date: 0-0-2007 0:0 revision:0 [head]

PMID-7521083 Modulatory functions of neurotransmitters in the striatum: ACh/dopamine/NMDA interactions.

  • in striatum, 2 basic classes of neural transmission:
    • fast neural transmission:
      • glutamate response in striatum to cortical/thalamic input via AMPA on medium spiny neurons
      • GABA output of the striatum
    • modulatory neural transmission:
      • NMDA
      • DA dopamine
      • substance P
      • ACh acetylecholine (large aspiny neurons, 30um soma! 1-2% of the population)
  • input to the cholinergic large aspiny neurons
    • GABA/substance P medium-spiny neurons which project to SNr + GPi
    • DA neurons from tegmentum, a8 a9 a10 groups
    • Glu neurons in the thalamus, and, to a lesser extent, from the cortex
  • DA D2 autoreceptors inhibit/regulate the release of DA, and it can also modulate the release of ACh + glu
    • specifically D2 has been demonstrated to inhibit ACh release, but not D1 (accourse)
  • figure 2 is kinda nice for the neurotransmitters in the basal ganglia
  • not really all that clear of an article