Basal ganglia (Chapter 19)

Question 1

The principal components of the basal ganglia (aka basal nuclei) are:

Answer 1

Putamen
Caudate
Nucleus accumbens
Globus pallidus (internal and external segments)
Subthalamic nucleus
Substantia nigra (pars compacta, pars reticulata)

Question 2

Describe the loop for basal ganglia circuitry, at its most basic level:

Answer 2

Cortex –> basal ganglia –> thalamus –> cortex

Question 3

Afferents [inputs] to the striatum from the cortex use _________ as their nt and are _________.

Answer 3

Glutamate; excitatory

Question 4

Efferents [outputs] from the striatum, GPe, GPi, and SNr from the cortex use _________ as their nt and are _________.

Answer 4

GABA; inhibitory

Question 5

Dopaminergic outputs from the SNc are inhibitory to the __________ pathway and excitatory to the __________ pathway.

Answer 5

Indirect; excitatory

SNc outputs mnemonic: INhibitory, INdirect

Question 6

Outputs of the STN are _________ and use __________.

Answer 6

Excitatory; glutamate

Question 7

The lenticular nucleus consists of the:

Answer 7

Globus pallidus (ext. and int.)
Putamen

Question 8

The striatum consists of the:

Answer 8

Caudate
Nucleus accumbens
Putamen

(ventral striatum: + basal forebrain)

Question 9

Describe the basic direct pathway.

Answer 9

When a signal to initiate movement is sent from the cerebral cortex to the basal ganglia, it leads to the silencing of neurons in the GPi (and SNr). This frees the thalamus from the inhibitory effect of the GPi, allowing movement to occur.

Cortex (+) –> striatum (-) –> GPi (-) –> thalamus (+) –> cortex.

Question 10

Describe the basic indirect pathway.

Answer 10

The indirect pathway leads to increased suppression of movements. The striatum receives excitatory output from the cortex. The striatum then sends inhibitory projections to the GPe. The GPe sends inhibitory projections to the STN, which sends excitatory projections to the GPi (and SNr). This increases the inhibitory effect of the GPi (and SNr) on the thalamus, leading to increased suppression of movements via the thalamus’s inhibitory effect on the cortex.

Question 11

How do the two parts of the substantia nigra differ in their roles in the basal ganglia circuitry?

Answer 11

The SNr is one of the basal output nuclei and has inhibitory effects on the thalamus.
The SNc has a more widespread modulatory role via DA projections to other parts of basal nuclei: inhibitory to the indirect pathway and excitatory to the direct pathway.

Question 12

Where are enkephalins found in the striatum?

Answer 12

Striosomes - chemical compartments.

Enkephalins are endogenous opioid peptides that bind to opioid receptors and are involved in pain regulation.

Question 13

Outputs from the GPi are always inhibitory, with increased inhibition in the __________ pathway and decreased inhibition in the __________ pathway.

Answer 13

Indirect; direct

Question 14

The STN receives inhibitory inputs from the _________ and excitatory inputs from the __________.

Answer 14

GPe; cortex

Question 15

STN outputs are excitatory to the __________ and ________.

Answer 15

Globus pallidus (both internal and external); SNr

Question 16

Which regions are connected by the subthalamic fasciculus?

Answer 16

STN across internal capsule to GP

Question 17

The GPi and thalamus are connected via two white matter pathways, the _________ and _________.

Answer 17

Lenticular fasciculus; ansa lenticularis

Question 18

Name the 3 different cortical areas involved in the 3 parallel loops through the basal ganglia circuitry:

Answer 18

Frontal/association areas
Sensorimotor areas
Limbic areas

Question 19

The circuit that involves limbic areas features inputs to the striatum, specifically the ________.

Answer 19

Ventral striatum/nucleus accumbens

Question 20

The circuit that involves frontal/association areas features inputs to the striatum, specifically the ________.

Answer 20

Caudate

Question 21

The circuit that involves sensorimotor areas features inputs to the striatum, specifically the ________.

Answer 21

Putamen

Question 22

Which pathway is affected by STN damage, and what is the result?

Answer 22

Damage to the STN affects the indirect pathway and results in positive motor signs/involuntary movements (e.g., Huntington’s).

Question 23

Why does damage to the STN result in involuntary movements?

Answer 23

Because of loss of excitatory inputs from the STN to the GPi results in failure to inhibit the thalamus, causing increased cortical activation.

Question 24

What happens when you remove DAergic inputs to the direct and indirect pathways (both in terms of circuits and motor outcomes)?

Answer 24

Removing DAergic inputs to the direct and indirect pathways results in increased thalamic inhibition and decreased cortical output –> negative motor signs (bradykinesia, hypokinesia)

Question 25

Name some examples of positive motor movements.

Answer 25

Babinski, snout reflexes Epilepsy Hypertonia ("cogwheeling") Tremors (PD), chorea, athetosis, ballisms (HD)

Question 26

Name some examples of negative motor movements.

Answer 26

``` Paralysis Hypotonia, dysmetria Bradykinesea (slow movements) Hypokinesia (lack of movements) Ataxia (cerebellar pts, ALS) ```

Question 27

How are the basal nuclei [ganglia] supplied with bloodflow?

Answer 27

The basal nuclei are supplied by perforating branches of the Circle of Willis. Globus pallidus: Anterior choroidal artery Striatum: MCA (lenticulostriate arteries) SN and STN: Posterior cerebral/posterior communicating arteries

Question 28

Describe the pathology of Huntington's disease.

Answer 28

HD is a hereditary disorder in which patients show constant, involuntary movements (i.e., chorea) which get progressively worse, followed by dementia and personality changes. The chorea is thought to be caused by degeneration of the striatum, while the cognitive and affective symptoms are thought to be caused by caudate-cortical degeneration.

Question 29

If a patient is displaying hemiballismus, where would you expect the striatal lesion to be?

Answer 29

Contralateral STN

Question 30

Describe the pathology of Parkinson's disease.

Answer 30

Loss of DA neurons in the SNc lead to brady- and hypokinesia, as decreased DAergic inputs from the SNc cause decreased activity in the direct [excitatory] pathway and increased activity in the indirect [inhibitory] pathway.

Question 31

How are the VTA and nucleus accumbens involved in reward?

Answer 31

The VTA and nucleus accumbens are part of the reward circuit, which has both DAergic and serotonergic pathways. A rewarding stimulus elicits DA release in the VTA --> NA --> PFC (regulates motivation and incentive salience in cortex.)

Question 32

What is it about opiates that makes heroin (and other narcotics) so rewarding? How is this different than effects of cocaine?

Answer 32

Opiates bind to opiate receptors in the nucleus accumbens, which decreases GABA (normally inhibits DA release) and allows more DA to be dumped into the synaptic cleft. On the other hand, cocaine blocks the reuptake of DA, which has the same net result of increasing DA in the synaptic space.

Question 33

What is the difference between tolerance, dependence, and addiction, including their respective mechanisms?

Answer 33

Tolerance: Need increasing amounts of drug to get same effect, as enzymes that break down the drug are unregulated. Dependence: Need drug to function normally; without it, withdrawal symptoms [physiological reactions] occur. Adaptation occurs such that neurons adapt to repeated drug exposure and only function normally in its presence. *Mediated by thalamus/brainstem Addiction: Compulsive drug craving after exposure to drug. *Mediated by mesolimbic/reward pathway