Transient compartmentalization of interneuron dendrites.

Abstract

Much of our understanding of the delicate interplay between synaptic input, dendritic voltage-gated channels and spike backpropagation comes from a relatively small sampling of cortical or hippocampal principal cell types, whose large diameter apical dendrites permit electrophysiological manipulation combined with imaging approaches (Stuart et al. 1999). Although the dendrites of local circuit interneurons possess voltage-gated channels influential in action potential (AP) initiation and timing (Martina et al. 2000; Kaiser et al. 2001), their functional properties are poorly understood. In this issue of The Journal of Physiology, Goldberg et al. (2003a,b) combine two-photon imaging with whole-cell recording and anatomical reconstruction to examine calcium dynamics during AP backpropagation and subthreshold synaptic stimulation in dendrites of three types of primary visual cortex (V1) supragranular interneurons: multipolar parvalbumin positive ‘fast spikers’ (FS), bipolar calretinin-positive ‘irregular spikers’ (IS) and a heterogeneous group of ‘adapting cells’ (AD). In all interneurons, somatically generated APs actively backpropagated into the dendrites and evoked instantaneous calcium transients confirming the presence of voltage-gated sodium, potassium and calcium channels. However, in contrast to neighbouring pyramidal neurons, single APs rarely evoked detectable calcium signals and only when trains of stimuli were applied were appreciable calcium transients detected. The calcium signal in interneuron dendrites during a 10 AP (40 Hz) train was comparable to that activated by a single pyramidal cell backpropagating spike. Consistent with the high endogenous buffering capacity of interneurons (Kaiser et al. 2001) the decay time constant of the interneuron calcium transients was also significantly slower (IS > FS) than in pyramidal cells. The spatial extent of calcium transients was not uniform across the interneuron dendritic trees and they were typically observed only at proximal dendritic locations (< 100 μm) despite the confirmed presence of voltage-gated calcium channels throughout their dendrites. This spatial control was mediated by A-type transient outward potassium currents and was mitigated by previous synaptic activity in a manner reminiscent of that described for principal cells (Hoffman et al. 1997). Interestingly, blockade of transient A-type potassium channels was without effect on proximal calcium transients and suggests that like pyramidal cells, the transient potassium channel density in V1 interneurons increases with distance from the soma. This contrasts with the uniform density of 4-AP/TEA-sensitive channels observed on hippocampal somatostatin-positive interneurons (Martina et al. 2000) and underscores that few general assumptions can be applied to the diverse population of inhibitory interneurons. K+ currents on interneurons are important in regulating both synaptic activation and spike initiation (Fricker & Miles 2000) and these data suggest that A-type transient currents on V1 interneurons regulate both spike initiation and propagation. The present data highlight a hitherto unrecognized functional compartmentalization of interneuron dendrites: a perisomatic domain where backpropagating APs influence propagation of both electrical and calcium signals perhaps via gap junctions, and a distal compartment which backpropagating spikes reach only following inactivation of dendritic potassium channels. Given the afferent-specific innervation of proximal versus distal dendritic locations by thalamic and intracortical glutamatergic afferents respectively, the functional compartmentalization of interneuron dendrites may serve to additionally increase their computational prowess. Turning their attention to subthreshold synaptic stimuli, Goldberg et al. report that the predominant dendritic calcium signal in IS and AD cells arises via activation of synaptic NMDA receptors following AMPA receptor-driven depolarization. However, in FS cells, blockade of NMDA receptors removed only a small (and variable) calcium component to reveal a kinetically distinct calcium signal generated by Ca2+-permeable (CP-) AMPA receptors. CP-AMPA receptor-mediated synaptic events possess rapid kinetics and enable tight coincidence detection in interneuron populations. Accordingly, calcium influx kinetics in FS cells was more rapid than either IS and AD cells. Of particular note, in all three cell types synaptic activation generated calcium signals typically restricted to ≈10-20 μm of dendritic space, suggesting that despite the absence of spines, the synaptic calcium signal will remain highly localized. How this is achieved is unclear but this functional compartmentalization is probably highly significant given that kinetically distinct afferent projections can target overlapping dendritic domains of interneuron dendrites (Walker et al. 2002). Thus, the present papers demonstrate yet another tantalizing aspect of interneuron physiology and suggest that FS cells (and other cells that possess CP-AMPA receptors) may sustain multiple spatially isolated calcium domains that are independent of the background depolarization required for NMDA receptor-mediated calcium signals. Moreover, the different requirements for calcium entry via NMDA versus CP-AMPA receptors may provide the discriminatory mechanism for activation of downstream molecular targets and the plastic processes currently being studied in interneuron populations.