Cortical and Thalamic Input into Striatal Cholinergic Interneurons

Striatal cholinergic interneurons play an important role in regulating striatal output, possibly through the modulation of local inhibitory circuits. These neurons have been implicated in a number of movement disorders including Parkinson's disease which affects around 127,000 people in the UK1. Currently there is no cure for Parkinson's but there are a number of treatments available which can slow the progression of the disease.

In Parkinson's disease diminished striatal dopaminergic signalling leads to increased release of acetylcholine by interneurons, distorting network function and inducing structural changes that contribute to symptoms. The hope is a better understanding of microcircuit dysfunction may lead to new therapeutic strategies for the treatment of striatal-based movement disorders, like Parkinson's.

A group from the University of Oxford have been researching the mechanisms underlying cholinergic interneuron responses to motivationally salient stimuli (a neural stimulus that has acquired an association with primary reinforcement often leading to useful adaptive behaviours).

Striatal cholinergic interneurons are commonly believed to be "tonically active neurons" (TANs) in behaving animals. Their multiphasic responses are particularly sensitive to motivationally sensitive stimuli. They usually respond with a pause in their tonic firing, often followed by an increase in spiking. The group hope that elucidating how this dynamic spiking of the striatal cholinergic interneurons is governed by their myriad of synaptic inputs will lead to a better understanding of their functional roles in striatal microcircuits and contributions to adaptive behaviour.

In a paper recently published in the Journal of Neuroscience, principal investigator Natalie Doig and the Oxford group used in vivo electrophysiology techniques and the Scientifica IVM (in vivo micromanipulator), to investigate how cortical and thalamic excitation mediate multiphasic responses of striatal cholinergic interneurons.

The group established that an individual cholinergic interneuron can form synapses with axon terminals arising from both the cortex and the thalamus. Cortical inputs were sparser than thalamic inputs but despite this the group showed that brief, single-pulse electrical stimulation of the cortex often evoked short–latency spiking. They also found that short-latency interneuron responses to matched stimulation of thalamus showed similar timings to those driven by cortical inputs but were less robust. However, interneuron responses to thalamic inputs became increasingly robust with each pulse of a high-frequency stimulus train, whereas responses to cortical inputs were progressively dampened.

The group also recorded the multiphasic responses of monkey TANs to motivationally salient stimuli, demonstrating their correlation to the results found in rats for initial spiking, pause, and rebound response phases. These correlations between TAN response phases were present after reward-predicting stimuli but not after unpredicted rewards, raising the possibility that the two behavioural conditions recruited distinct sets of inputs to differentially influence firing.

The groups conclude that their results show "the cortex and the thalamus can provide an initial synaptic excitation that shapes the multiphasic responses of cholinergic interneurons to motivationally salient stimuli under specific behavioural conditions".

Ref:

1 = Parkinson's UK: http://www.parkinsons.org.uk/content/facts-journalists

Paper details:

Natalie M. Doig, Peter J. Magill, Paul Apicella, J. Paul Bolam, and Andrew Sharott (2014) Cortical and Thalamic Excitation Mediate the Multiphasic Responses of Striatal Cholinergic Interneurons to Motivationally Salient Stimuli The Journal of Neuroscience: 34(8):3101–3117 DOI:10.1523/JNEUROSCI.4627-13.2014

http://www.ncbi.nlm.nih.gov/pubmed/24553950

Find out more about Dr Sharott's research:

http://www.mrc.ox.ac.uk/people/dr-andrew-sharott

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