Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit
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1
Ecole Normale Supérieure, France
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2
University of Sheffield, United Kingdom
The striatum, the principal input structure of the basal ganglia, is crucial to both motor control and learning. It receives convergent input from all over neocortex, hippocampal formation, amygdala and thalamus, and is the primary recipient of dopamine in the brain. Within the striatum is a GABAergic microcircuit that acts upon these inputs, formed by the dominant medium-spiny projection neurons (MSNs) and fast-spiking interneurons (FSIs). There has been little progress in understanding the computations it performs, hampered by the non-laminar structure that prevents identification of a repeating canonical microcircuit. We sought to solve this problem by searching for dynamically-defined computational elements within a full-scale model of the striatum. In the process, we have made significant progress in large-scale modelling of this structure. We constructed a new three-dimensional model of the striatal microcircuit’s connectivity, implemented at 1:1 scale, neuron-for-neuron. The anatomical model was instantiated with our new dopamine-modulated neuron models of the MSNs and FSIs. A new model of gap junctions between the FSIs was introduced and tuned to experimental data. Finally, we developed a novel spike-train clustering method, suitable for large-scale models; applying this to the outputs of the model allowed us to find groups of synchronised neurons at multiple time-scales. We found that, with realistic in vivo background input, small assemblies of synchronised MSNs spontaneously appeared, consistent with experimental observations. The number of assemblies and the time-scale of synchronisation were strongly dependent on the simulated concentration of dopamine. Such small cell assemblies, forming spontaneously only in the absence of dopamine, may contribute to motor control problems seen in humans and animals following loss of dopamine cells. We dissected the contributions of the circuit elements to the formation of the cell assemblies, and found that the FSI input was crucial in desynchronising the MSN activity. We also showed that feed-forward GABAergic input from the FSIs counter-intuitively increases the firing rate of the MSNs. Our interpretation of these results is that, in healthy striatum, localised, phasic changes of FSI activity switch the type of computations performed by MSNs. A phasic increase in local FSI activity would, in turn, increase the local MSN responses to ongoing cortical input, performing a striatum-wide "selection" computation on cortical inputs without using winner-takes-all. By contrast, a phasic decrease in local FSI activity would, for the same MSNs, promote competition between them through their network of inhibitory local collaterals. Thus, striatal FSIs seem able to set the scale and type of MSN computation.
Conference:
Computational and Systems Neuroscience 2010, Salt Lake City, UT, United States, 25 Feb - 2 Mar, 2010.
Presentation Type:
Poster Presentation
Topic:
Poster session III
Citation:
Humphries
M,
Wood
R and
Gurney
K
(2010). Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit.
Front. Neurosci.
Conference Abstract:
Computational and Systems Neuroscience 2010.
doi: 10.3389/conf.fnins.2010.03.00238
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Received:
04 Mar 2010;
Published Online:
04 Mar 2010.
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Correspondence:
Mark Humphries, Ecole Normale Supérieure, Paris, France, mark.humphries@manchester.ac.uk