Basal ganglia Flashcards
What is the basal ganglia
An extrapyramidal, subcortical system for the selection of internally generated, goal-driven motor programmes
Summary of unctions of basal ganglia- competition
Solves a competing input selection problem- plans, motivations and context
Summary of functions of basal ganglia- selection
Select goal, select actions to promote goal, seelct movements in response to salient stimuli
Summary of functions of basal ganglia- reinforcement learning
Learn outcome of actions and their cues, to adapt behaviour to achieve appropriate and efficient responses to the environment
What are the 4 components of the basal ganglia
Striatum, globus pallidus, subthalamic nucleus, substantia nigra
What is the striatum split into
Caudate, putamen (split by the internal capsule)
What is the globus pallidus split into
External (GPe), internal (GPi)
What is the substantia nigra split into
Pars compacta (SNc), pars reticulata (SNr)
How does info from the cortex first enter the basal ganglia
Cortex -> Striatum
What neurons in the striatum receive most of the afferent input from the cortex
Striatal medium spiny neurons- the principal neuron of the striatum
What is firing of striatal medium spiny neurons correlated with
Cues for movement or intended movement, not movement itself
What neurotransmitter identity are striatal medium spiny neurons
GABAergic
What are the 2 types striatal medium spiny neurons
D1- have dopamine D1 receptors
D2- have dopamine D2 receptors
What do D1 striatal medium spiny neurons express
Substance P and dynorphin opioid
What expression do D2 striatal medium spiny neurons have
Express enkephalin opioid, have A2A receptors
What does it mean to say the basal ganglia is an extrapyramidal system
The tracts of the basal ganglia don’t pass directly through the pyramids of the medulla oblongata aka don’t directly execute movement
Where does the striatum output to
Substantia nigra pars reticulata (SNr)/internal globus pallidus (GPi) and external globus pallidus (GPe)
What are the output nuclei of the basal ganglia
Substantia nigra pars reticulata (SNr) and internal globus pallidus (GPi)
What is the neurotrasmitter identity of output from the basal ganglia
GABAergic neurons
What are the 2 output pathways of the basal ganglia
‘ASCENDING’- to VLo/VA
‘DESCENDING’- to upper brainstem eg SC, RF, PPN
By what principle does the basal ganglia modulate the thalamocortical relay
Principle of disinhibition
How do striatal neurons to SNr/GPi disinhibit the thalamocortical relay
Normally, SNr/GPi cells fire tonically and inhibit the thalamus
Striatal stimulation inhibits the SNr/Gpi, disinhibiting activity in thalamocortical relay neurons
What are the 2 pathways through the basal ganglia
DIRECT- striatum->SNr/GPi
INDIRECT- striatum-> Gpe->STN->SNr/GPi
What is the organsation of direct/indirect pathway projections in the striatum
Direct/indirect pathway projections are intermingled within the striatum
What output does the substantia nigra pars compacta (SNc) do
Ascending dopamine input to the striatum
What is the result of striatal excitation in the DIRECT PATHWAY
Striatum inhibits SNr/GPi, reduced GPi inhibition of thalamus
Facilitates movement
What is the result of striatal excitation in the INDIRECT PATHWAY
Striatum inhibits GPe, reduced GPe inhibition of STN
Excitation in STN excites the GPi, increasing its inhibition of the thalamus
Inhibits movement
Which of the direct vs indirect pathways facilitates vs inhibits movement
DIRECT PATHWAY- faciliates movement
INDIRECT PATHWAY- inhibits movement
How do D1 and D2 receptors segregate in the direct vs indirect pathway
Direct pathway- D1 receptors
Indirect pathway- D2 receptors
What is the effect of dopamine on the direct pathway
D1 DA receptors on direct striatal projections FACILITATE the pathway, facilitating movement
What is the effect of dopamine on the indirect pathway
D2 DA indirect striatal projections INHIBIT the pathway, facilitating movement
What effect does dopamine from SNc have on the direct and indirect pathway
FACILITATES MOVEMENT IN BOTH PATHWAYS
Facilitates the direct pathway, inhibits the indirect pathway
List some examples of basal ganglia diseases
Parkinsons’, drug-induced Parkinsons, Huntingsons, Tourettes
OVERALL symptoms of basal ganglia diseas
Deficiency of movement, involuntary movements
Symptoms of basal ganglia disease- deficiency of movement examples
Akinesia, bradykinesia
Symptoms of basal ganglia disease- involuntary movements examples
Tremor at rest, dystonias, chorea, tics, dyskinesias
Primary motor symptoms of Parkinsons
Akinesia, tremor at rest, rigidity, postural instability (TRAP)
Non-motor dysfunction in Parkinsons
Problems with sleep behaviour, depression, cognition, pain, dementia, bowels
What neuronal changes underlie Parkinsons
Progressive loss of SNc DA neurons (DA facilitates movement)
Proteinaceous aggregations
What are proteinaceous aggregations in Parkinsons
Lewy bodies- intraneuronal cytoplasmic inclusions
Major components are a-synuclein and ubiquitin
How does the intrinsic physiology of SNc neurons promote their vulnerability to Parkinsons
Very highly arborised means high metabolic demand
Oxidative stress, neuroinflammation, protein misfolding and accumulation
Environment contributions to Parkinsons
Neuroinflammation, pesticides + genetics, toxin exposure (MPTP toxicity)
What causes MPTP toxicity
Selective entry of MPP+ into DA neurons leads to downstream increase of ROS (reactive oxygen species) via DA dumping, causing selective death
What key drug treatment is used for Parkinsons
L-DOPA (precursor of dopamine) PLUS an inhibitor of peripheral decarboxylase
Increased dopamine production
How is L-DOPA problem as a treatment for Parkinsons
On/off effects, gait freezing, LDOPA induced dyskinesia typically occur within 5-10 years of LDOPA therapy
Alternative Parkinsons therapy options to LDOPA
DA agonists, gene therapy, transplans, DBS
How does deep brain stimulation work
Stimulating electrode implanted during surgery into basal ganglia nuclei eg STN, GP
High frequency stimulation
Symptoms of Huntington’s chorea
Usually hyperkinetic
Chorea, dystonia, rigidity and cognitive decline
What changes occur to brain structure in Huntington’s chorea
Striatal atrophy-loss of caudate nucleus GABAergic medium spiny neurons (particularly D2)
Cortical atrophy
Underlying causes of Huntington’s disease
Genetics, ‘codon-repeat disease’ that encodes consecutive polyglutamines from huntingtin gene (HTT), HTT protein aggregates
How do brain structure changes in Huntington’s cause its hyperkinetic phenotype
D2 neurons especially affected, meaning the direct pathway dominates the indirect pathway, causing decreased inhibition of the thalamus
Treatments for Huntingtons
Antidopaminergics, tetrabenazine, neuroleptics, benzodiazepines
Where does the thalamus project to
The frontal lobe, the same areas that provided the basal ganglia with input
What is the neurotransmitter identity of STN output
Glutamatergic
What are the maps in the basal ganglia like
Topographical maps of the area of cerebral cortex they receive input from
Some of these cortex areas receive input from the other lobes
Examples of basal ganglia-thalamocortical circuits
Skeletomotor, oculomotor, prefrontal, limbic circuit
What is the cortico-basal-thalamocortical motor circuit
Sensorimotor cortical fields -> putamen -> motor portions of GPi and SNr -> VLo/VA in thalamus -> M1/SMA/PM
What subcortical feedback loop is involved in the cortico-basal thalamocortical motor circuit
The GPi and SNr also project to the centromedian nucleus of the thalamus -> putamen
How does the basal ganglia output map onto M1/SMA/PM
Separate populations of neurons in specific areas of the basal ganglia structures (and thalamus) project to the M1, SMA and PM- the cortical subcircuits remain segregated
What motor roles has the motor circuit of the basal ganlglia been implicated in
Action/goal selection, preparation for movement, initiation desired movement, inhibiting unwanted movements, sequencing of movement
How may the basal ganglia act as a focusing model?
Simultaneous activation of the direct pathway and indirect pathway facilitates intended movements and suppresses competing ones
Issues with the basal ganglia focusing model- not anatomically supported
Requires indirect pathway to target large areas of the pallidum to prevent unwanted movements while the direct pathway acts on small areas of the GPi to selectively facilitate selected ovement- not supported by anatomical evidence
Neural activity of basal ganglia- movement preparation
Monkey basal ganglia motor areas in delayed-response tasks shows changes in firing frequency when desired movement direction is cued
Neural activity of basal ganglia- movement execution
Some basal ganglia neurons change their firing rate in relation to the onset of movement, suggesting they are concerned with movement execution
Neural activity of basal ganglia- scaling movement
Activity changes in GPi correlate with amplitude and velocity of movement, while some correlate with overall direction of movement, suggesting role in higher-aspects of movement
What neurons in the basal ganglia are associated with reinforcement motor learning
Many DA neurons in SNc that project to the striatum are correlated with behaviour reinforcement cues
Cholinergic interneurons in the striatum have their tonic activity reduced by rewards/noxious stimuli
What are the respective roles of dopaminergic input and cholinergic intereurons in the striatum in motor learning
Cholinergic interneurons signal MSNs about the OCCURANCE of salient stimuli, while dopaminergic inputs signal the behavioural VALUE of stimuli
What is the reward prediction error
A discrepancy between the expectation of a reward and its delivery
What signals the reward prediction error
Changes in the activity of DA cells- DA release strengthens synapses involved in generating the rewarded behaviour, reinforcing that behaviour
How can DA and ACh affect the strength of synapses in the basal ganglia
LTP, LTD, or spike-time dependent modulation
What abnormality of neuronal activity may underlie Parkinsons
Abnormal burst discharges and firing patterns, unusual oscillatory neuronal activity
What frequency oscillation is associated with Parkinsons
High amplitude alpha/beta frequency oscillation in the STN and GPi- may prevent oscillations at higher gamma band frequencies, needed for normal movement
How may DBS work by providing high-frequency stimuliation
Replaces the irregular abnormal basal ganglia output with a more regular tolerable pattern, or disrupts abnormal beta frequency oscillations
