Striatal Fast-Spiking Interneurons: From Firing Patterns to Postsynaptic Impact

Abstract

In the striatal microcircuit, fast-spiking (FS) interneurons have an important role in mediating inhibition onto neighboring medium spiny (MS) projection neurons. In this study, we combined computational modeling with in vitro and in vivo electrophysiological measurements to investigate FS cells in terms of their discharge properties and their synaptic efficacies onto MS neurons. In vivo firing of striatal FS interneurons is characterized by a high firing variability. It is not known, however, if this variability results from the input that FS cells receive, or if it is promoted by the stuttering spike behavior of these neurons. Both our model and measurements in vitro show that FS neurons that exhibit random stuttering discharge in response to steady depolarization do not show the typical stuttering behavior when they receive fluctuating input. Importantly, our model predicts that electrically coupled FS cells show substantial spike synchronization only when they are in the stuttering regime. Therefore, together with the lack of synchronized firing of striatal FS interneurons that has been reported in vivo, these results suggest that neighboring FS neurons are not in the stuttering regime simultaneously and that in vivo FS firing variability is more likely determined by the input fluctuations. Furthermore, the variability in FS firing is translated to variability in the postsynaptic amplitudes in MS neurons due to the strong synaptic depression of the FS-to-MS synapse. Our results support the idea that these synapses operate over a wide range from strongly depressed to almost fully recovered. The strong inhibitory effects that FS cells can impose on their postsynaptic targets, and the fact that the FS-to-MS synapse model showed substantial depression over extended periods of time might indicate the importance of cooperative effects of multiple presynaptic FS interneurons and the precise orchestration of their activity.

Target Selectivity of Feedforward Inhibition by Striatal Fast-Spiking Interneurons

“…Stimulation with trains of light pulses (10 Hz, 2 ms, Fig. 2D) induced depressing synaptic responses, similar to previously reported direct connections between FS interneurons and MSNs (Planert et al, 2010;Gittis et al, 2011;Klaus et al, 2011). The dynamic properties of light-evoked synaptic responses were quantified using a model for synaptic dynamics Tsodyks et al, 1998) (see Materials and Methods) and compared with direct FS-MSN connections recorded in the same animals (n ϭ 13 synaptically connected pairs).…”

Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model

“…The FD formalism dictates that the synaptic strength is updated by the product of facilitating (F) and depressing (D) variables/factors. This description shows quantitatively good approximations of experimentally measured synapse dynamics (Tsodyks and Markram, 1997; Markram et al, 1998; Planert et al, 2010; Klaus et al, 2011; Lindahl et al, 2013). The model formalism assumes a finite pool of synaptic resources in active ( y ), inactive ( z ), and recovered ( x ) states.…”

Different correlation patterns of cholinergic and GABAergic interneurons with striatal projection neurons

“…FSI-MSN connections show substantial depression during continuous discharge (Klaus et al, 2011). The lack of evidence for monosynaptic inhibition between spikes of FSIs and MSNs could also reflect the high discharge rate of FSIs in behaving animals (unlike slice preparations), thus leading to prolonged synaptic depression of the MSNs (see discussion in Gage et al, 2010).…”