Uncoordinated firing rate changes of striatal fast-spiking interneurons during behavioral task performance

Abstract

Basal ganglia circuits make key contributions to decision making. Distributed, synchronous feedforward inhibition of striatal medium spiny neurons by fast-spiking GABAergic interneurons (FSIs) has been argued to be important for the suppression of unwanted actions, and a deficit in FSIs has been found in human patients with Tourette syndrome. However, no studies have yet examined how striatal FSIs change their activity during behavioral tasks. Here I describe 36 presumed striatal FSIs recorded in rats during well practiced performance of a radial maze win-stay task. Although most FSIs showed robust task-related activity, the temporal patterns of firing rate change were highly idiosyncratic. In contrast to other classes of striatal neurons, FSIs showed little or no coordinated population response to major task events such as instruction cues or rewards. Even when multiple FSIs were recorded simultaneously from the same local region of striatum, firing rate changes were dissimilar, and no clear evidence for synchronous firing was found using cross-correlograms (18 FSI pairs examined). These results suggest that FSIs play a more complex role in the information processing achieved by striatal microcircuits than supposed by current theoretical models.

Figure 1.

Win–stay task and striatal cell classification. A, Plus-maze arrangement (to scale). Thirsty rats ran continuously between water ports at the arm ends. As the rat approached the central zone on each trial, one pair of lights began flashing to indicate which arm choice would be rewarded. B, Striatal neurons fall into distinct classes based on waveform characteristics [see also Fig. 2 and Berke et al. (2004)]. Most striatal neurons had wide waveforms (blue dots) and were not tonically active; these are presumed MSNs. One set of tonically active cells had very brief waveforms (red dots) and are presumed fast-spiking GABAergic interneurons. Another, rarely encountered set of tonically active neurons (green dots; “O cells”) with distinctive waveforms may represent another interneuron class (see Results). Black circles indicate unclassified neurons. Mean peak width, valley width, and session-wide firing rate for each cell class were as follows: MSNs, 141 μs, 474 μs, 1.39 Hz; FSIs, 87 μs, 144 μs, 24.7 Hz; O cells, 128 μs, 252 μs, 15.2 Hz. Six additional unclassified units were excluded from this plot because unusually complex waveform shapes prevented unequivocal assignment of “peak” and “valley” labels to waveform components.

Figure 2.

Distinct activity patterns and behavioral correlates of presumed striatal neuron subpopulations. A, Five examples each of FSIs (top), O cells (middle), and MSNs (bottom), showing recording locations in striatum and spike waveforms (left; mean ± SD). B, Interspike interval (ISI) histograms during task performance (awake) and SWS, for the same units as shown in A. y-Axis is counts per bin (starting at zero). FSIs showed an early peak (marked with asterisk) in the ISI histogram during sleep. C, Corresponding raster plots (top panels) and perievent time histograms (bottom panels) aligned on arrivals at the baited reward port. Numbers at left of histograms indicate firing rate (in hertz; scales begin at zero); numbers at right of rasters indicate trial number. Examples illustrate the wide range of distinct firing rate changes observed for FSIs and MSNs, whereas all O cells had similar firing rate time courses. The top three FSIs were recorded simultaneously from the same tetrode in dorsal striatum, demonstrating that nearby FSIs can have very different patterns of behavior-linked firing rate change.

Figure 3.

Distinct population activity patterns of three different striatal subpopulations. A, Mean normalized firing rate for MSNs (n = 109), FSIs (n = 36), and O cells (n = 5) relative to instruction cue onset (left) or arrival at baited reward ports (right). At the population level, relatively little change was seen for FSIs because they show very different responses from each other (Fig. 2). In contrast, the similarity of O cell responses produces a sharp population activity increase after rewards. B, Averaged firing maps for each subpopulation (left, MSNs; middle, FSIs; right, O cells). The maxima of the color scales are 2.3, 28, and 22 Hz, respectively.