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61 Cards in this Set
- Front
- Back
Inputs to striatum |
Dopaminergic from substantia nigra, pars compacta D1 receptor - excitatory (Gs) D2 receptor - inhibitory (Gi/O coupled) Cerebral cortex glutamatergic input |
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Direct pathway of basal ganglia |
D1 neurons have direct GABAergic projection to output part of basal ganglia, the internal globus pallidus. Internal pallidum then has inhibitory GABAergic projection to thalamus. Thus, D1 activation by cerebral cortex and striatum leads to disinhibition of the thalamus. Thalamus has excitatory glutamatergic projections to cerebral cortex, promoting movement. |
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Indirect pathway of basal ganglia |
D2 has GABAergic inhibitory projection to external globus pallidus, which in turn has GABAergic inhibitory projection to subthalamic nucleus. Disinhibited subthalamic nucleus excites internal globus pallidus. Internal pallidum inhibits thalamus via GABAergic projection. Thalamus then inhibits cortex to inhibit movement. |
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Parkinson's Disease |
Lose dopamine neurons in substantia nigra, pars compacta. Loss of dopaminergic tone in the striatum. Promotes the indirect pathway (actually not true - creates poison pattern of synchronous events leading to simultaneous activation of "go" and "no go" = ridigity) |
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Block D2 Dopamine receptor with haloperidol antipsychotic |
Parkinsonism due to dopamine receptor supersensitivity Causes tandive dyskinesia |
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Unilateral lesion in suthalamic nucleus |
Results in contralateral ballistic movement - hemiballismus |
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Basal ganglia definition |
Series of interconnected subcortical structures that process reentrant cortical information for successful execution of action (and cognitive) sequencing, timing and selection; a functionality that allows for smooth, accurate, purposeful movements (and thoughts) with optimal posture that can be perfected through repetition. |
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Caudate nucleus Putamen Globus pallidus, external and internal segments Subthalamic nuclei Substantia nigra pars compacta Subthalamic nucleus |
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Neostriatum |
Caudate + putamen Essentially same structure bisected by white matter |
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Output nuclei of basal ganglia |
Internal globus pallidus Sustantia nigra pars reticulata |
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Rostral view of basal ganglia |
Putamen and head of caudate bisected by internal capsule |
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Lenticular nucleus |
Putamen + globus pallidus |
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Corpus striatum |
Caudate + Putamen + accumbens + globus pallidus |
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Striatum |
Caudate, putamen, accumbens |
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Eye Saccade circuit from basal ganglia |
Internal pallidus also has GABAergic input to superior colliculus, which controls eye saccades. |
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Supplemental motor area feedback loop |
Supplementary motor area sends input to striatum, goes through basal ganglia, and heads back to same part of cortex. |
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Reentrant cortical input |
Topographical Motor cortex projects to one part of striatum, to one part of globus pallidus and substantia nigra to one part of thalamus, for instance. |
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What part of cortex projects to basal ganglia |
Almost every cortical region, with exception of auditory cortex and primary visual cortex (weak projections) |
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Huntington's Disease |
Arises from degeneration of output cells of striatum, medium spiny neurons, that give rise to direct and indirect pathway. Age of onset is 30-40 years Trinuleotide repeat Motor dysfunction, choreiform movements |
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Pattern of events in Huntington's disease |
Early on, dysplasticity - plastic patterns that usually do not occur are occuring - more than degeneration. Later, degeneration including of cortex occurs, leading to cognitive symptoms like psychosis/hallucination, dementia, anxiety, and depression. |
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Hemiballismus |
Results from unilateral lesion to subthalamic nucleus. Results in ballistic movements on contralateral side of body, causing injury and fatigue. |
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Neurotransmitter release from dopaminergic substantia nigra pars compacta neurons |
Co-release dopamine and GABA |
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Thalamus also projects to striatum. |
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Serotonergic input onto basal ganglia |
All parts of basal ganglia receive serotonergic input from dorsal raphe nucleus |
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Noradrenergic input onto basal ganglia |
All of basal ganglia except caudate and putamen receive noradrenergic input from locus ceruleus. |
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Baseline firing of caudate and putamen |
Do not fire at rest until receive stimulus from cerebral cortex |
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Baseline firing of substantia nigra pars compacta |
Fire at 2 Hz at rest, undergo bust of phasic firing of 20 Hz with novel stimulus or reward. Interface between motor function and reward. |
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Baseline firing of globus pallidus external segment |
Part of indirect pathway. Has irregular firing of 10-70 Hz |
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Baseline firing of globus pallidus internal segment |
Tonic firing of 60-80 Hz. Movement related |
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Baseline firing of subthalamic nucleus |
Tonic firing of 20 Hz, movement-related. |
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Firing in direct pathway when cortex active and inactive |
Inactive cortex -> inactive striatum. Tonically active globus pallidus which inhibits thalamus. No output to UMNs in cortex. Active cortex -> active striatum. Tonically active globus pallidus is inhibited, which releases inhibition on thalamus so thalamus is active. Excited upper motor neurons in cortex. |
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Disinhibitory basal ganglia circuit for eye saccades |
Active cortex -> active caudate nucleus (striatum). Inhibits substantia nigra pars reticularis output pathway, which disinhibits superior colliculus causing eye movements. |
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Synapse between caudate nucleus and substantia nigra pars reticulata |
GABA/inhibitory |
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Synapse between Substantia nigra parts reticulata and superior colliculus |
GABA/inhibitory |
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Disinhibitory circuit of direct pathway |
Cortical inputs excite striatum which inhibits globus pallidus to disinhibit thalamus, driving excitation of motor cortex UMNs. |
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Striatum |
Input nucleus of basal ganglia Site of enormous convergence, must also have tons of processing. Large dendritic trees on principal projection neurons. |
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Ratio of cells in parts of basal ganglia |
Cortex - 150,000,000 Striatum - 30,000 (500:1) Globus Pallidus external - 100 (300:1) Globus Pallidus internal - 1 (100:1) |
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Morphology of striatal medium spiny neurons |
Large dendritic trees studded with many dendritic spines. Each spine receives cortical input, neck of spine receives dopaminergic input. |
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Number of synapses on each medium spiny neuron |
10,000 cortex synapses onto each medium spiny neuron |
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Inputs on Medium Spiny Neurons |
Cortex - glutamatergic Intralaminar nuclei of thalamus - glutamatergic Fast spiking interneurons - GABA Low threshold spiking interneurons - GABA Other medium spiny neurons - GABA Globus pallidus - GABA Cholinergic interneurons in striatum - ACh Substantia nigra pars compacta - Dopamine Dorsal raphe nucleus - Serotonin |
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Population of medium spiny neurons in striatum |
95% of cells in striatum |
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GABAergic inputs onto medium spiny neurons |
Fast spiking interneurons - GABA Low threshold spiking interneurons - GABA Other medium spiny neurons - GABA Globus pallidus - GABA |
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Glutamatergic inputs onto medium spiny neurons |
Cortex - glutamatergic Intralaminar nuclei of thalamus - glutamatergic |
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Types of medium spiny neurons |
D1 expressing - direct pathways - send projections directly to output structures via internal pallidus D2 expressing - indirect pathway - globus pallidus external to subthalamic to internal pallidus to thalamus. |
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Three basal ganglia circuits |
1) Direct 2) Indirect 3) Hyperdirect pathway |
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Hyperdirect pathway |
Information directly fed into subthalamic nucleus, which communicates to internal pallidus, thalamus, then cortex. |
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Direct and indirect pathways of basal ganglia |
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Compartments within striatum |
Patch - express mu opioid receptor. Process limbic inputs. Matrix - devoid of mu opioid receptors. Process motor inputs. Also differential expression of acetylcholinesterase between the two. |
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Organization of basal ganglia cell firing |
Basal ganglia "chunks" information. Instead of encoding each individual component, different basal ganglia cells fires either beginning of sequence, during sequence, or at end of sequence.
E.x. - if mice presses lever 6 times, some dopaminergic neurons fire at first press, some right before first press, some at last press, some at beginning and end. |
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Role of dopaminergic neurons in substantia nigra |
Appear to be active at start or stop of action - may explain inability to start or stop movements in Parkinson's disease. |
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Parkinson's disease |
Loss of dopaminergic neurons in substantia nigra pars compacta (causing loss of dopaminergic tone in striatum). Causes bradykinesis, rigidity, tremor at rest, and impairment of action initiation and termination. Other symptoms - festination (shuffling gait), postural instability, pain, depression, autonomic dysfunction, and sleep disruption. |
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Effect of dopamine in striatum |
Controls corticostriatal plasticity Glutamatergic input from cortex on D1 or D2 spiny neurons. When dopamine binds to receptor on MSN, induces long-term depression of glutamate release from cortex presynaptic terminal. |
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Conditions needed for LTD of corticostriatal synapse |
1. D2 dopamine receptor tone 2. Glutamate release from cortex cell hitting mGluR5 3. Ca2+ entry into postsynaptic cell after striatum depolarizes. |
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Mechanism of dopamine effect on corticostriatal plasticity |
Dopamine binding to D2 receptor results in production of endocannabanoid that retrogradely hits presynaptic CB1 receptor which is GiO coupled. Results in LTD of glutamate release from presynaptic cortical cell. |
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Effect of monoamine depletor and D2 agonist on plasticity. |
Strength of synapse at baseline is 100% Treat with reserpine which depletes monoamine stores so no dopamine - then do not observe plasticity If treat with both reserpine and quinpriole (agonist of D2 receptors), do get LTD |
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Effect of dopamine neuron toxin on plasticity |
Treat with dopamine neuron toxin (6-OHDA) -> no plasticity Rescue with quinpriole (agonist of D2 receptors) = LTD |
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Effect of URB597 (inhibits endocannabanoid degradation) on plasticity |
Boost endocannabanoid levels. Induce LTD even without dopamine. |
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Effect of dopamine neuron toxin on movement |
if treat with 6-OHDA, animals cannot move. If treat with UR597 (endocannabanoid booster), also cannot move. If add quinpriole (D2 agonist) as well, then animal can move |
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Caudate vs putamen functions |
Caudate - dorsomedial striatum - responsible for goal directed action. When goal is gone, action halts. Putamen - dorsolateral striatum. Responsible for habit-formation or stimulus-response action strategies. |
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Basal ganglia influence in cognition |
Mediate action selection and sequencing for cognition as well as movement. Parkinson's - dementia and depression Huntington's - dementia, depression, psychosis Schizophrenia - psychosis Tourette's syndrome - echolalia, palilalia, corprolalia OCD - intrusive, compulsive thoughts ADD - impulsivity/"dyskinesia of thought" |
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How are striatum neurons organized to perform actions? |
Neuron ensembles - groups of neurons - in striatum fire synchronously to control a particular action. Same organization downstream - i.e. in globus pallidus. |