PMID-14607789[0] The subthalamic nucleus in the context of movement disorders
- this is a good anatomy article, very descriptive -- almost too much information to grapple with.
- STN = important structure for the modulation of activity of basal ganglia structures
- STN is anterior-adjacent to the red nucleus
- The average number of neurons in each STN nucleus varies from species to species and has been estimated to be ~25 000 in rats, 35 000 in marmosets, 155 000 in macaques, 230 000 in baboons and 560 000 in humans
- The volume of the STN is ~0.8 mm3 in rats, 2.7 mm3 in marmosets, 34 mm3 in macaques, 50 mm3 in baboons and 240 mm3 in humans.
- Number of neurons does not scale with volume, uncertain why not.
- STN is divided into three functional units: motor, associative, and limbic cortical regions innervate, respectively motor, associative, and limbic regions of the striatum, pallidium SNr.
- they give a complete list of these 3 in 'intrinsic organization of the STN'
- STN is divided into 2 rostral thirds and one cauldal third.
- medial rostral = limbic and associative
- lateral rostral = associative
- dorsal = motor circuits. (the largest part, see figure 2)
- hence, the anterodorsal is thought to be the most effective target for DBS.
- STN is populated primarily by projection neurons
- the dendritic field of a single STN neurons can cover up to one-half of the nucleus of rodents
- efferent projections (per neuron, branched axons)
- GPe, GPi, SNr 21.3%
- GPe and SNr 2.7%
- in both segments of the pallidum, projections are uniformly arborized & affect an extensive number of cells.
- GPe and GPi 48%
- GPe only 10.7%
- 17.3% remaining toward the striatum
- most of the cortical afferents to the STN arise from the primary motor cortex, supplementary motor area, pre-SMA, and PMd and PMv; these target the dorsal aspects of the STN.
- afferents consist of collaterals from the pyramidal tract (layer 5) & cortical fibers that also innervate the striatum (latter more prevalent). afferents are glutamergic.
- ventromedial STN recieves afferents from the FEF (area 8) and suppl.FEF (9)
- GPe projects extensively to STN with GABA. see figure 3 [1]
- almost every cell in the STN resonds to pallidal GABAergic stimulation.
- 13.2% of GPe neurons project to GPi, STN, and SNr
- 18.4% to GPI and STN,
- 52.6% to only the STN and SNr
- 15.8% remaining to the striatum.
- DA afferents from the SNc
- ACh from the tegmentum
- Glutamergic afferents from the centromedian thalamus (CM)
- Serotonin from the raphe nucleus
- fibers from the tegmentum, SNc, motor cortex, VM.pf of the thalamus, and dorsal raphe synapse on distal dendrites
- pallidal inhibitory fibers innervate mostly proximal dendrites and soma.
firing properties:
- about half of STN neurons fire irregularly, 15-25% regularly, 15-50% burst.
- bursting is related to a hyperpolarization of the cell.
- movement-related neurons are in the dorsal portion of STN and are activated by either/both active/passive movements of single contralateral joints
- there is a somatotopic organizaton, but it is loose.
- many units are responsive to eye fixation, saccadic movements, or visual stim. these are in the ventral portion.
- activation of the STN drives SNr activity, which inhibits the superior colliculus, allowing maintainance of eye position on an object of interest.
- ahh fuck: if high currents are delivered to STN or high concentrations of GABAergic antagonists are applied abnormal movements such as dyskinesias can be elicited
- low concentrationns of GABA antagonists induces postural asymmetry and abnormal movements, but no excessive locomotion.
- dyskinesias result from high-frequency or high-current stimulation to the STN! low frequency stimulation induces no behavioral effects. [2]
- small (<4% !!) lesions cause focal dystonias
- in parkinsonian patients, activity in the STN is characterized by increased synchrony and loss of specificity in receptive fields + mildly increased mean firing rate.
- 55% of STN units in PD patients respond to passive movements, and 24% to ipsilateral movements (really?) - indicative of the increase in receptive field size caused by the disease.
____References____
[0] Hamani C, Saint-Cyr JA, Fraser J, Kaplitt M, Lozano AM, The subthalamic nucleus in the context of movement disorders.Brain 127:Pt 1, 4-20 (2004 Jan) |
[1] Sato F, Lavallée P, Lévesque M, Parent A, Single-axon tracing study of neurons of the external segment of the globus pallidus in primate.J Comp Neurol 417:1, 17-31 (2000 Jan 31) |
[2] Beurrier C, Bezard E, Bioulac B, Gross C, Subthalamic stimulation elicits hemiballismus in normal monkey.Neuroreport 8:7, 1625-9 (1997 May 6) |
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