Activity-dependent changes in the firing properties of neocortical fast-spiking interneurons in the absence of large changes in gene expression

Abstract

The diverse cell types that comprise neocortical circuits each have characteristic integrative and firing properties that are specialized to perform specific functions within the network. Parvalbumin-positive fast-spiking (FS) interneurons are a particularly specialized cortical cell-type that controls the dynamics of ongoing activity and prevents runaway excitation by virtue of remarkably high firing rates, a feature that is permitted by narrow action potentials and the absence of spike-frequency adaptation. Although several neuronal intrinsic membrane properties undergo activity-dependent plasticity, the role of network activity in shaping and maintaining specialized, cell-type-specific firing properties is unknown. We tested whether the specialized firing properties of mature FS interneurons are sensitive to activity perturbations by inactivating a portion of motor cortex in vivo for 48 h and measuring resulting plasticity of FS intrinsic and firing properties with whole-cell recording in acute slices. Many of the characteristic properties of FS interneurons, including nonadapting high-frequency spiking and narrow action potentials, were profoundly affected by activity deprivation both at an age just after maturation of FS firing properties and also a week after their maturation. Using microarray screening, we determined that although normal maturation of FS electrophysiological specializations is accompanied by large-scale transcriptional changes, the effects of deprivation on the same specializations involve more modest transcriptional changes, and may instead be primarily mediated by post-transcriptional mechanisms.

Figure 1

Muscimol released chronically from ELVAX implants abolishes spontaneous activity in vivo. 100µm ELAX slabs containing either muscimol or saline were implanted on the cortical surface (top panel) and multiunit activity was recorded 24 and 48 hours later (middle and bottom panels) to determine the degree and extent of inactivation. Multiunit records obtained beneath the ELVAX implants indicate an absence of activity at both superficial and deep recording sites exposed to muscimol (black traces), whereas rhythmic activity typical of ketamine anesthesia was intact under the saline implant (grey traces).

Figure 2

Developing and mature FS interneuron firing properties are activity-dependent. A. Voltage traces from FS cells exposed to saline or muscimol in vivo between P16 and P18. Inset traces are on an expanded time base and illustrate the effects of inactivation on spike width, firing rate, and AHP. Activity-deprived cells were adapting, had lower maximum firing rates, and issued broader action potentials than saline-exposed control cells. B. The effect of inactivation on firing properties is evident in the population data: ISI ratio and maximum firing rate are significantly reduced in muscimol-exposed cells, and spike width is significantly increased, but measures of intrinsic excitability are unchanged. C. Mature FS firing properties are also affected by inactivation between P25 and P27. D. ISI ratio and maximum firing rate are slightly and significantly reduced by inactivation, and the intrinsic excitability of FS cells is markedly increased due to increased R_In and consequently decreased rheobase.