Encoding Network States by Striatal Cell Assemblies

Abstract

Correlated activity in cortico-basal ganglia circuits plays a key role in the encoding of movement, associative learning and procedural memory. How correlated activity is assembled by striatal microcircuits is not understood. Calcium imaging of striatal neuronal populations, with single-cell resolution, reveals sporadic and asynchronous activity under control conditions. However, N-methyl-d-aspartate (NMDA) application induces bistability and correlated activity in striatal neurons. Widespread neurons within the field of observation present burst firing. Sets of neurons exhibit episodes of recurrent and synchronized bursting. Dimensionality reduction of network dynamics reveals functional states defined by cell assemblies that alternate their activity and display spatiotemporal pattern generation. Recurrent synchronous activity travels from one cell assembly to the other often returning to the original assembly; suggesting a robust structure. An initial search into the factors that sustain correlated activity of neuronal assemblies showed a critical dependence on both intrinsic and synaptic mechanisms: blockage of fast glutamatergic transmission annihilates all correlated firing, whereas blockage of GABAergic transmission locked the network into a single dominant state that eliminates assembly diversity. Reduction of L-type Ca2+-current restrains synchronization. Each cell assembly comprised different cells, but a small set of neurons was shared by different assemblies. A great proportion of the shared neurons was local interneurons with pacemaking properties. The network dynamics set into action by NMDA in the striatal network may reveal important properties of striatal microcircuits under normal and pathological conditions.

Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit

“…We apply our multiple spiketrain analysis to the outputs of this model to find groups of synchronised neurons at multiple time-scales. We then show that, with realistic in vivo background input, small assemblies of synchronised MSNs spontaneously appear, consistent with experimental observations (Carrillo-Reid et al, 2008), and that the number of assemblies and the time-scale of synchronisation is strongly dependent on the simulated concentration of dopamine.…”

“…For our present purposes, we wanted to find groups of co-active or mutually antagonistic MSNs that could form the basis for competitive dynamics within the striatum. In addition, we studied this input regime to see if the reported striatal cell clusters spontaneously formed in vitro (Carrillo-Reid et al, 2008) could be identified in our model. However, analysis methods suitable for exploratory analysis of such large spike-train data-sets are lacking (Brown et al, 2004).…”

“…out dopamine Spontaneously formed striatal cell assemblies were observed using calcium imaging by (Carrillo-Reid et al, 2008), from an in vitro preparation that was excited by bath application of an NMDA agonist. To see if we could observe equivalent dynamics in our model, we began with a model without dopamine, setting φ 1 = φ 2 = 0, so that the model was close to this in vitro state.…”

“…Such problems are at the cutting-edge of current neuroscience research. Recent multielectrode experimental techniques (Buzsaki, 2004;Miller & Wilson, 2008) and calcium imaging (Carrillo-Reid et al, 2008) are already identifying hundreds of neurons, and there is a clear need for suitable multi-unit methods (Brown et al, 2004), as their absence places a fundamental limit on the use of such large-scale data.…”

“…We have shown here that the algorithm can successfully find a wide range of groups that differ in number, size, discreteness of firing, and time-scale of activation. Extending this approach to determine neurons shared between more than one cell assembly (Carrillo-Reid et al, 2008), and to improve detection of groupings at multiple time-scales is the subject of ongoing work.…”