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The basal ganglia: a functional approach

“But, what is it for?”

Finding out with computational neuroscience

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Phenomenology● Damage to BG is main cause of:

■ Parkinson’s disease✴ Bradykinesia, akiensia, tremor

■ Huntington’s disease✴ Involuntary movements (when slow and extended = chorea)

● Damage to BG implicated in: ■ ADHD

✴ Attention deficit hyperactivity disorder

■ Schizophrenia✴ Complex condition with positive symptoms (e.g. delusions) and

negative symptoms (e.g. lack of affect)

PD video

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Rationale for tackling the problem● If brain area/system X is damaged, what are

the consequences?

● Strategy: find out the main function of X.

● Then, understanding of the phenomena will be unified: each deficit is an aspect of loss of the main function of X.

● So, what do the basal ganglia do….?

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Action selectionPredisposing conditions (sensory input, cognitive state,

homeostasis, etc)

Energy balance (A1: feeding)

Fluid balance (A2: drinking)

Threat (A3: escape)

Motor resources

Behavioural output (feeding)

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Cognitive example● Students in this lecture

■ ‘shall I pay attention or think about plans for this evening’? [‘action’ of defining cognitive state]

■ ‘pay attention or act on my being hungry’■ but then fire alarm goes off….

● Salience issues (again)

● ‘lower’ and ‘higher’ level processing■ social protocols and long term planning versus

biological drives and homeostasis■ Probably mediated by cortical and sub-cortical

centres respectively

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Mediating competition between actionsCentral switch has a ‘wiring’ advantage over the ‘distributed’ alternative

A1

A1 A1

A1

Distributed (all-to-all) connectivity.

Number of connections ~ N2

A1

A1 A1

A1

S

Central switchNumber of connections ~

N

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Hypothesis for basal ganglia function

● basal ganglia is the central ‘switch’ in the vertebrate brain that enables ‘action’ selection

■ Here ‘action’ may mean ‘internalised behaviour’ defined by cognitive state

● Therefore disorders of the basal ganglia are disorders of action selection

■ E.g. PD, HD = inability to select motor actions appropriately

■ E.g. ADHD, Schiz. = inability to suppress unwanted actions or cognitive states

Redgrave ,et al. 1999

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Evidence for this hypothesis: 1If the action selection hypothesis is true then we require that …

1. The BG must take input from a wide variety of brain areas• i.e. putative ‘command centres’ for ‘action requests’• These should be cortical and subcortical

2. There must be some mechanism by which the BG can switch on selected motor resources

3. There must be evidence of a flow of information between command centres, BG, and associated motor centres

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Evidence for this hypothesis: 2

If the action selection hypothesis is true then we require that …

4. The BG must understand be able to extract the ‘salience’ of each request• Assuming that this is done in BG and is not sent

separately (otherwise we have a repeat of the ‘wiring argument’ )

5. There must be evidence of neuronal selection mechanisms in BG

Subsequent slides will be related back to these points by labels of the form E#

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Basal ganglia input E1

putamen

head of caudatetail of caudate

globuspallidus

The main input nucleus isneostriatum (or sometimes simply the striatum) composed of the putamenand caudate nuclei.

The striatum is by far the largest nucleus in the basal ganglia and receives input from all over the brain including: all of cerebral cortex (except primary sensory areas) and subcorticalnuclei such as the superior colliculus (via the intralaminarthalamus)

Also shown is the globuspallidus (see next slide for details)

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Disinhibition gating hypothesis 1: basic mechanism

E2

striatum

GPi/SNr

striatum

GPi/SNr

Output nuclei of the BGGPi = globus pallidus internal segmentSNr = substantia nigra pars reticulata

Cortex

BGThalamus

subcorticalmotor nuclei

Tonic inhibition

Alexander,et al. 1990

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Disinhibition gating hypothesis 2: data with glutamate injections in striatum

E2

striatum

SNr

VM

SC

VM = ventromedial thalamus

SC =superior colliculus(midbrain sensory and motor motor nucleus)

Alexander,et al. 1990

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Representing discrete actions 1: cortico-basal ganglia loops

Cortex

BGThalamus

BrainstemMotor nuclei

Five main loops according to primary cortical input area

E3

‘Motor’ (supplementary motor area – SMA)

‘Oculomotor’ (frontal eye fields – FEF)

‘Prefrontal 1’ (dorsolateral prefrontal cortex – dlPFC)

‘Prefrontal 2’ (lateral orbitofrontalprefrontal cortex – LOF)

‘limbic’ (anterior cingulate area – ACA)

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Representing discrete actions 2: topography in BG

E3

Different body parts represented by different parts of BG and related structures

We conclude (from this slide and the last) that BG represents actions in discrete channels

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Representing discrete actions 1: sub-cortical-basal ganglia loops

E3

Sub-cortical structures include:

Superior colliculus (SC)

Pedunculopontine tegmental area(or simply peduncularpontinenucleus - PPN)

Periaqueductal gray (PAG)

Sub-cortical structures

BG

Intra-laminar thalamus

BrainstemMotor nuclei

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Disinhibition gating and channels Predisposing conditions E2 & E3

Ctx1: action1 Ctx2: action2

BGThalamus

Motor resourcesfor action 1

Motor resourcesfor action 2

Probably some shared

resources

BGThalamus

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Interlude – the anatomy

output nuclei

Coronalsection

putamen

head of caudatetail of caudate

globuspallidus

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Salience extraction in striatumE4Medium spiny neurons

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Spines up close…

AT

Sp

DS

textbookPaul Bolam’s lab

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Selection mechanisms in BG 1: basic idea

Cortical inputs

‘striatum’ Note: ‘striatum’is both excitatory and inhibitoryResolved later...

Output (GPi/SNr)

E5

inhibition excitation Model neuron

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Selection mechanisms in BG 2: realistic Instantiation in basal ganglia

Striatum

input

STN

output

Diffuseprojection

striatum STN

inputs

‘output layer’

Assumes diffuse projections from STN = subthalamic nucleus

- +

E5

Mink and Thach,1993

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Focussed and diffuse connectivityMedium spiny neuron

STN neuron

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Striatal structure and BG architecture

Mainly D1 dopamine receptors

Mainly D2 dopamine receptors

NB – red/blue do NOT signify excitation/inhibition here

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Instantiation in basal ganglia: 2E5

Selectionpathway

Striatum (D1)

Cortex/thalamus

STN

EP/SNr

BG output Function?

?Striatum (D2)

Cortex/thalamus

STN

GPe

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New functional architecture:selection and control pathways

Interpret GPefferents as

control signals for modulating

selection pathway

Gurney et al, 2001

Striatum (D1)

Cortex/thalamus

STN

EP/SNr

Striatum (D2)

GP

E5

Selection pathway Control pathway

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Simulation - basic selection dynamics

salience

EP/SNr output

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Comparison with prevailing model: ‘Direct’ and ‘Indirect’ pathways

Cortex/thalamus

STN

EP/SNr

Striatum (D2)

GP

Striatum (D1)

Direct

Indirect• Never instantiated quantitatively

• No global selection

Selection

Control

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Summary● Action selection is a key computational problem for

all animals.● Central switching appears to be an optimal solution● The BG appears well placed to do this in vertebrates

because■ It receives widespread input (cortical and subcortical)■ Tonic inhibition and its selective release appear to be a

mechanism for gating motor programmes■ Functional loops and topography support the idea of action

‘channels’.■ Medium spiny neurons could act to extract salience■ There is a multitude of selection mechanisms in BG,

including that supported by the innervation of SNr/GPi from striatum and STN.

● Under our hypothesis, disorders of the basal ganglia are understood as disorders of action selection

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Suggested reading● The chapter in Squire et a (Fundamental

Neuroscience)

● The review by Mink (1996)

● Our paper outlining the action selection hypothesis (Redgrave et al 1999)

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ReferencesAlexander, G. E. and M.D., C. (1990): Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends in Neuroscience 13, 266-271.

Redgrave, P., Prescott, T. J. and Gurney, K. (1999): The basal ganglia: a vertebrate solution to the selection problem? Neuroscience 89, 1009-1023.

Mink, J. W. and Thach, W. T. (1993): Basal ganglia Intrinsic circuits and their role in behavior. Current Opinion in Neurobiology 3, 950-957.

Gurney, K., Prescott, T. J. and Redgrave, P. (2001): A computational model of action selection in the basal ganglia I: A new functional anatomy. Biological Cybernetics 84, 401-410.

Gurney, K., Prescott, T. J. and Redgrave, P. (2001): A computational model of action selection in the basal ganglia II: Analysis and simulation of behaviour. Biological Cybernetics 84, 411-423.

Mink, J. W. (1996): The basal ganglia: Focused selection and inhibition of competing motor programs. Progress in Neurobiology 50, 381-425.

Squire, L. R., M. J., Bloom, McConnell, S.K., Roberts, J. L. Spitzer, N.C. and Zigmond,, F. E. (2003): Fundamental Neuroscience, Academic Press. Chapter 31