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[0] Froemke RC, Merzenich MM, Schreiner CE, A synaptic memory trace for cortical receptive field plasticity.Nature 450:7168, 425-9 (2007 Nov 15)

[0] Shidara M, Aigner TG, Richmond BJ, Neuronal signals in the monkey ventral striatum related to progress through a predictable series of trials.J Neurosci 18:7, 2613-25 (1998 Apr 1)

[0] Pollak P, Benabid AL, Gross C, Gao DM, Laurent A, Benazzouz A, Hoffmann D, Gentil M, Perret J, [Effects of the stimulation of the subthalamic nucleus in Parkinson disease]Rev Neurol (Paris) 149:3, 175-6 (1993)

[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: -0 tags: nucleus accumbens caudate stimulation learning enhancement MIT date: 09-20-2016 23:51 gmt revision:1 [0] [head]

Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning

  • Monkeys had to learn to associate an image with one of 4 reward targets.
    • Fixation period, movement period, reward period -- more or less standard task.
    • Blocked trial structure with randomized associations + control novel images + control familiar images.
  • Timed stimulation:
    • Nucleus Accumbens during fixation period
      • Shell not core; non-hedonic in separate test.
    • Caudate (which part -- targeting?) during feedback on correct trials.
  • Performance on stimulated images improved in reaction time, learning rate, and ultimate % correct.
  • Small non-significant improvement in non-stimulated novel image.
  • Wonder how many stim protocols they had to try to get this correct?

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ref: Hashimoto-2003.03 tags: DBS STN subthalamic nucleus globus pallidus electrophysiology date: 03-07-2012 21:57 gmt revision:3 [2] [1] [0] [head]

PMID-12629196[0] Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons

  • why does STN stim work? investigated the effects of STN HFS on neuronal activity of GPi and GPe.
  • monkeys were treated with MPTP
  • used a scaled-down version of human DBS stimulator (cool!)
  • high frequency stimulation resulted in stimulus-synchronized regular firing pattern, plus an overall increase in pallidal firing rate.
    • they think that this synchrony may underlie the beneficial effect of HFS in the STN
  • only behavior was, apparently, what amplitude and frequency were required to alleviate parkinsonian symptoms.
  • if i do DBS in normal monkeys, is there anything to say that the effect will be similar or comparable to treatment stimulation?
  • they remind us that HFS = lesion in terms of alleviating symptoms of parkinsons.

____References____

[0] Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL, Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons.J Neurosci 23:5, 1916-23 (2003 Mar 1)

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ref: Carpenter-1981.11 tags: STN subthalamic nucleus anatomy tracing globus_pallidus PPN substantia_nigra DBS date: 02-22-2012 22:01 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-7284825[0] Connections of the subthalamic nucleus in the monkey.

  • STN projects to both segments of the globus pallidus in a laminar and organized fashion.
    • most fibers projected to the lateral pallidal segment (aka GPe).
  • also projected to specific thalamic nuclei (VAmc, VLm, DMpl).
  • the major projection of PPN is to SN.
  • striatum projects to the substantia nigra pars reticulata (SNr). interesting.
  • see also: PMID-1707079[1]
    • "Anterograde transport in fibers and terminal fields surrounded retrogradely labeled cells in the LPS (GPe), suggesting a reciprocal relationship [to the STN]"
  • These data suggest that the STN receives its major subcortical input from cell of the LPS (GPe) arranged in arrays which have a rostrocaudal organization.
  • No cells of the MPS (GPi) or SN project to the STN.
  • The output of the STN is to both segments of the GP and SNpr.
  • Major subcortical projections to PPN arise from the MPS (GPi) and SNpr (output of the BG) , but afferents also arise from other sources.
    • The major projection of PPN is to SN.
    • HRP injected into PPN produced profuse retrograde transport in cells of the MPS and SNpr and distinct label in a few cells of the zona incerta and STN.

____References____

[0] Carpenter MB, Carleton SC, Keller JT, Conte P, Connections of the subthalamic nucleus in the monkey.Brain Res 224:1, 1-29 (1981 Nov 9)
[1] Carpenter MB, Jayaraman A, Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents.J Hirnforsch 31:5, 653-68 (1990)

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ref: Hamani-2004.01 tags: STN subthalamic nucleus movement disorders PD parkinsons basal_ganglia globus_pallidus anatomy DBS date: 02-22-2012 15:03 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

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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ref: Fellows-2006.04 tags: parkinsons subthalamic nucleus thalamus DBS STN force velocity overshoot grasp date: 02-22-2012 14:51 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-16549385[0] The effect of subthalamic nucleus deep brain stimulation on precision grip abnormalities in Parkinson's disease

  • Deep Brain stimulation improves mobility/dexterity and dyskinesia of patients in general, via an increase in rate and decrease in reaction time, but it does not let the patient match force output to the object being manipulated (that is, the force is too large).
  • The excessive levels of grip force present in the stimulation 'off' state, and present from the early stages of the disease, however, were even more marked with STN stimulation on.
    • STN DBS may worsen the ability to match force characteristics to task requirements. (position control is improved?).
    • quite fascinating.

See also PMID-19266149[1] Distal and proximal prehension is differentially affected by Parkinson‘s disease The effect of conscious and subconscious load cues

  • asked PD and control patients to lift heavy and light objects.
  • While controls were able to normalize lift velocity with the help of both conscious and subconscious load cues, the PD patients could use neither form of cue, and retained a pathological overshoot in lift velocity.
  • Hence force control is remarkably affected in PD, which is consistent with the piper rhythm being absent / usually present for isometric contraction.

____References____

[0] Fellows SJ, Kronenbürger M, Allert N, Coenen VA, Fromm C, Noth J, Weiss PH, The effect of subthalamic nucleus deep brain stimulation on precision grip abnormalities in Parkinson's disease.Parkinsonism Relat Disord 12:3, 149-54 (2006 Apr)
[1] Weiss PH, Dafotakis M, Metten L, Noth J, Distal and proximal prehension is differentially affected by Parkinson's disease. The effect of conscious and subconscious load cues.J Neurol 256:3, 450-6 (2009 Mar)

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ref: Lee-2005.07 tags: STN subthalamic nucleus hemiballismus DBS date: 01-26-2012 17:24 gmt revision:3 [2] [1] [0] [head]

PMID-16032642[0] Common causes of hemiballism.

  • stroke of the STN results in hemiballismus - wild movements of the limbs. recall the input to the STN is inhibitory from GPe, and the output is exitatory to the GPi. chemical treatment is via dopamine blockade (1976!)
  • hemiballism is rare, but usually associated with lesion to the contralateral STN.
    • however, half the cases of hemiballismus are associated with damage to the afferent or efferent pathways to the STN.
    • diabetes type 2 also commonly causes hemiballismus (hyperglycemia in asian women!)
  • hemiballismus is absent in sleep - the thalamocortical relay must be turned off.
  • hemiballismus is generally associated with high metabolic activity in the basal ganglia.
  • does this mean that stimulation to the STN in healthy monkeys will disinhibit large, possibly conflicting movements?
  • my thought: the subthalamic nucleus must be involved in the selection and regulation of appropriate movements.

____References____

[0] Lee HS, Kim SW, Yoo IS, Chung SP, Common causes of hemiballism.Am J Emerg Med 23:4, 576-8 (2005 Jul)

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ref: Bergman-1994.08 tags: subthalamic nucleus STN basal ganglia globus pallidus electrophysiology 1994 MPTP DBS date: 01-26-2012 17:19 gmt revision:3 [2] [1] [0] [head]

PMID-7983515[0] The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism

  • idea: record from STN and GPi before and after MPTP treatment in green monkeys.
  • recorded 4-8hz periodic activity (via autocorrelograms) in significantly more neurons from the MPTP treated animals in both the STN and GPi.
  • mean firing rate was increased in STN,
  • tremor-correlated cells found in both.
  • burst activity higher in both, too.
  • modulations in firing rate due to the application of flexion and extension torque pulses were higher in MPTP animals (duration and amplitude), in both areas.
  • spikes were longer in MPTP
  • no tyrosene hydroxylase activity in the PD mks.
  • PD tremor only frequently occurs in green mks following MPTP

____References____

[0] Bergman H, Wichmann T, Karmon B, DeLong MR, The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism.J Neurophysiol 72:2, 507-20 (1994 Aug)

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ref: Monakow-1978.11 tags: motor_cortex STN subthalamic nucleus anatomy DBS date: 01-26-2012 17:17 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-83239[0] Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey.

  • this paper is old and important!
  • The ipsilateral subthalamic nucleus receives a moderately strong and somatotopic organized projection from Woolsey's precentral motor cortex (PMd, M1 i guess)
    • No projections from the postcentral gyrus! (S1) (Is this still thought to be true?)
  • The remaining nucleus is occupied by less intensive projections from premotor and prefrontal areas
  • STN is a convergence site for pallidal and cortical motor/frontal projections.
  • autoradiography slices are damn hard for me to read.

____References____

[0] Monakow KH, Akert K, Künzle H, Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey.Exp Brain Res 33:3-4, 395-403 (1978 Nov 15)

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ref: Krack-2001.09 tags: STN subthalamic nucleus stimulation PD parkinsons DBS date: 01-24-2012 05:48 gmt revision:1 [0] [head]

PMID-11746616[0] Mirthful laughter induced by subthalamic nucleus stimulation.

  • high stimulation parameters induces mirthful laughter
  • prescribed parameters induced hypomanic behavior with marked improvement in akinesia.
  • STN must be involved in psychomotor as well as motor regulation.

____References____

[0] Krack P, Kumar R, Ardouin C, Dowsey PL, McVicker JM, Benabid AL, Pollak P, Mirthful laughter induced by subthalamic nucleus stimulation.Mov Disord 16:5, 867-75 (2001 Sep)

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ref: Lin-2006.12 tags: nucleus_basalis GABA ACh attention basal_forebrain sleep date: 12-07-2011 03:51 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-16928796[0] Fast modulation of prefrontal cortex activity by basal forebrain noncholinergic neuronal ensembles

in the author's own words:

  • in the intro sections, you can find the summary background info you need, both anatomical and functional. Despite the fact that most people think of this as solely the cholinergic projection system, my data is pointing to a very important role for the non-ACh projection system (most likely GABAergic!) in fast cortical modulation and ATTENTION. The relevant thing for you here is that, when people stimulated nucleus basalis and claimed the effect to be cholinergic, I believe most stimulation protocols (short bursts) are in fact mimicking the natural activity pattern of non-ACh projection system, and therefore should be re-interpreted with caution.
  • the intro, as promised, is concise, relevant, and has a lot of references.
  • key hypothesis is that the BF has GABA projections onto GABAergic interneurons in the PFC
    • typically, people focus on ACh projections.. perhaps as a matter of tradition?
    • PFC is reciprocally connected to the BF
  • secondary thing to test was the difference in behavior of the basal-forebrain tonic neurons (BFTN) between sleep and wake states.

____References____

[0] Lin SC, Gervasoni D, Nicolelis MA, Fast modulation of prefrontal cortex activity by basal forebrain noncholinergic neuronal ensembles.J Neurophysiol 96:6, 3209-19 (2006 Dec)

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ref: Froemke-2007.11 tags: nucleus basalis basal forebrain acetylcholine auditory cortex potentiation voltage clamp date: 10-08-2008 22:44 gmt revision:2 [1] [0] [head]

PMID-18004384[0] A synaptic memory trace for cortical receptive field plasticity.

  • nucleus basalis = basal forebrain!
  • stimulation of the nucleus basalis caused a reorganization of the auditory cortex tuning curves hours after the few minutes of training.
  • used whole-cell current-clamp recording to reveal tone-evoked excitatory and inhibitory postsynaptyic currents.
  • pairing of nucleus basalis and auditory tone presentation (2-5 minutes) increased excitatory currents and decreased inhibitory currents as compared to other (control) frequencies.
  • tuning changes required simultaneous tone presentation and nucleus basalis stimulation. (Could they indiscriminately stimulate the NB? did they have to target a certain region of it? Seems like it.)
    • did not require postsynaptic spiking!
  • Pairing caused a dramatic (>7-fold) increase in the probability of firing bursts of 2+ spikes
  • Cortical application of atropine, an acetylcholine receptor antagonist, prevented the effects of nucleus basalis pairing.
  • the net effects of nucleus basalis pairing are suppression of inhibition (20 sec) followed by enhancement of excitation (60 sec)
  • also tested microstimulation of the thalamus and cortex; NB pairing increased EPSC response from intracortical microstim, but not from thalamic stimulation. Both cortical and thalamic stimulation elicited an effect in the voltage-clamped recorded neuron.
  • by recording from the same site (but different cells), they showed that while exitation persisted hours after pairing, inhibition gradually increased commensurate with the excitation.
  • Thus, NB stimulation leaves a tag of reduced inhibition (at the circuit level!), specifically for neurons that are active at the time of pairing.

____References____

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ref: Shidara-1998.04 tags: ventral striatum nucleus accumbens monkey reward progress cue date: 03-27-2007 14:39 gmt revision:0 [head]

PMID-9502820[] Neuronal signals in the monkey ventral striatum related to progress through a predictable series of trials

  • neurons seem to cue/indicate/keep track of the state that a monkey is in during a sequence of reward-motivated behavior, e.g. there are neurons here which respond to the first trial, another group to anything other than 1st, others to first trial of schedules longer than one.
    • the recording site.

____References____

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ref: Pollak-1993.01 tags: DBS STN subthalamic nucleus original 1993 Benabid date: 03-12-2007 04:58 gmt revision:2 [1] [0] [head]

PMID-8235208[] Effects of the stimulation of the subthalamic nucleus in Parkinson disease

  • the original study! (in french:)
  • even back then, they used a quadripolar medtronic stimulating electrode w/ stimulation frequency of 130Hz.
  • how far have we come? not too far.

____References____

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ref: Dum-2003.01 tags: cerebellum dentate_nucleus projections cerebrum prefrontal posterior_pareital M1 PM thalamus somatotopic date: 03-11-2007 04:42 gmt revision:2 [1] [0] [head]

PMID-12522208 An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex

  • the dentate nucleus of the cerebellum projects to (at least four sections of if not all) of the cerebral cortex in a spatially-organized way.
    • dentate nucleus projects via the ventral anterior (VA) nucleus of the thalamus
    • dentate nucleus receives projections from the lateral hemispheres of the cerebellum (neocerebellum), which receives extensive collaterals from the pyramidal tract.

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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: thalamus basal ganglia neuroanatomy centromedian red nucleus images date: 0-0-2007 0:0 revision:0 [head]

http://www.neuroanatomy.wisc.edu/coro97/contents.htm --coronal sections through the thalamus, very nice!

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ref: GarciaRill-1991.01 tags: PPN pedunculopontine nucleus brainstem sleep locomotion consciousness 1991 date: 0-0-2007 0:0 revision:0 [head]

PMID-1887068 The Pedunculopontine nucleus

  • extensive review!