Cell types of Striatum

Question 1

What is the history of our understanding of SPNs/MSNs?

Answer 1

The spiny projection neurons were originally thought to be interneurons of the striatum due to their relatively small size when compared to aspiny cholinergic interneurons

However, injection of horseradish peroxide, a dye that undergoes retrograde transport, into the substantia nigra revealed staining of the MSNs, indicating that these were the output neurons of the striatum.

They were shown to be inhibitory through positive staining for GABA immunohistochemistry.

Question 2

List the properties of SPNs.

Answer 2

Spiny projection neurons:
- Account for 97% of the neurons in the straitum
- Are GABAergic
- Have soma of a medium size (15-20µm)

Question 3

What is local lateral inhibition

Answer 3

Local lateral inhibition describes how SPNs inhibit nearby SPNs in order to consolidate the large amount of information coming into the basal ganglia with the small output.
- Would indicate a loss of information, however the local lateral inhibition serves to retain this information.
- Thought to provide a basis for selection of behavioural channels eg: specific SPN activation allows the activation of specific agonist muscle to the correct extent

Question 4

What structure facilitates local lateral inhibition?

Answer 4

It is thought to be mediated by extensive projections from SPNs called the local axonal collaterals which can inhibit nearby SPNs.
- These occupy a similar volume to their dendrites

Question 5

What is the anatomical evidence for local lateral inhibition?

Answer 5

The size and relative density of the striatum is significantly larger than output nuclei
- This is an example of marked anatomical convergence (big structure -> small)
- Humans: 100million SPNs&raquo_space; 160,000 nRs in output
- Rats: 5.6million SPNs&raquo_space; ~ 60,000 in entopeduncular nucleus/SNpr

Anatomical evidence shows GABAergic synapses from SPNs present onto the dendrites of nearby SPNs
- Confirmed through injection of biocytin into synapse, which was retrogradely transport to other SPN

Question 6

What is the electrophysiological evidence for local lateral inhibition?

Answer 6

Ex vivo stimulation of SPN, whilst recording from adjacent SPN
- 2002 experiment showed that SPNs required ~200 firing events for an IPSP to be elicited
- No IPSP was observed in the presence of the GABA agonist bicuculline, which shows this interaction is GABA mediated.

Question 7

What are the characteristics of cholinergic interneurons/TANs?

Answer 7

TANs are tonically active (6-10Hz), large (soma = 20-50µm) and consist of less than 0.5% of the neuronal population in the striatum.

They have an extensive axonal arbour, which reaches 500µm from the soma, and facilitates connections with a large amount of SPNs.

Question 8

What inputs do TANs receive, and what information do these convey?

Answer 8

Their primary afferents (inputs) is from the parafascicular nucleus of the thalamus, and, to a relatively lesser extent, the cortex

• PFN input in thought to be important for normal movement
• Cortical input is thought to be important for reward-related movement

Question 9

What response do TANs exhibit, and how does this contribute to function?

Answer 9

TANs demonstrate a pause response where firing is transiently increased, then discontinued for ~200ms.
- Initial depolarisation occurs easily, as TANs have a resting membrane potential close to their AP threshold
- Long after-hyperpolarisation is variable and context dependent
**Prolonged (~200ms) – reward related learning
**Normal (~100ms) – movement related
This response typically occurs AFTER movement-related SPN-firing

Question 10

How do TANs functionally interact with SPNs in regards to movement?

Answer 10

In optimal voluntary movement the majority of SPNs are hyperpolarised. ACh release from TANs facilitates a slight depolarisation in SPNs, preparing them for activation in subsequent movements.

Question 11

What is the role of GABA/Parvalbumin neurons?

Answer 11

They act to produce another source of inhibition to SPNs in addition to local axonal collaterals.

Allows information to be retained in basal ganglia processing & allows specific fine-tuning of movement

Question 12

What do we know about GABA/calretinin neurons?

Answer 12

They are only found in the medial striatum, therefore are associated with limbic/memory selection

Question 13

What are the different names of GABA/somatostatin neurons?

Answer 13

NADPH-diaphorase (NOS)
Neuropeptide Y (NPY)

Question 14

What are the characteristics of GABA/somatostatin neurons?

Answer 14

• Compose less that 1% of neurons in the rat brain
• Persistent depolarisation
• Extensive and relatively unbranched axonal spread

Question 15

What are the inputs/outputs of somatostatin neurons?

Answer 15

Input: excitation from cortex
Output: SPNs and capillaries

Question 16

List the neurotransmitters/modulators contained within somatostatin neurons and their respective actions

Answer 16

Somatostatin (SON): excitation (assumed from action in cortex)

Neuropeptide Y (NPY): potent vasoconstrictor

Nitric oxide (NO): vasodilation, inhibition of SPNs

Question 17

How do each of the neurotransmitters released from SON interneurons play a role in movement?

Answer 17

SON: release activates anatomically distant but functionally connected SPNs to allows co-ordination of muscles in different regions.

NO: increases local blood flow to activated SPNs to ensure sufficient energy supply

NPY: decreases blood flow to inactivated SPNs to conserve energy