Putative cholinergic interneurons in the ventral and dorsal regions of the striatum have distinct roles in a two choice alternative association task

Abstract

The striatum consists of GABAergic projection neurons and various types of interneurons. Despite their relative scarcity, these interneurons play a key role in information processing in the striatum. One such class of interneurons is the cholinergic tonically active neurons (TANs). In the dorsal striatum, TANs are traditionally considered to be responsive to events of motivational significance. However, in recent years, studies have suggested that TANs are not exclusively related to reward and reward-predicting stimuli, but may contribute to other processes, including responses to aversive stimuli, detecting the spatial location of stimuli and generating movement. Currently there is little data concerning TAN activity in the ventral striatum (VS) of behaving animals. Here, we simultaneously recorded neurons in the ventral and the dorsolateral (DLS) regions of the striatum while animals performed a two choice alternative association task. Our data show that a large percentage of the putative TANs in both regions responded around movement initiation and execution. The majority of these neurons exhibited directional selectivity which was stronger in DLS relative to VS. In addition, the preferred directions in VS were mostly contralateral to the recording site whereas the observed preferred directions in DLS were equally distributed contralaterally and ipsilaterally to the recording site. The most interesting difference between DLS and VS was that DLS TANs maintained activity alterations throughout the movement whereas TANs in VS exhibited short-lasting phasic activity alterations that were maintained throughout the movement by different neurons. Our findings suggest that coding of movement by TANs in both regions overlaps to some degree, yet the differences in response patterns support the notion that the TANs in DLS participate in the motor loop whereas TANs in VS convey event-related information such as movement initiation, movement direction, and end of movement.

Keywords: cholinergic interneurons; chronic recording; dorsal striatum; motor control; movement coding; ventral striatum.

Figure 1

Recording electrodes were positioned in DLS and VS. (A,B) 60 micron sections showing electrode placement in DLS (A) and VS (B). Location of electrode tips as marked by electrolytic lesions are marked with black arrows. (C) Recording sites marked for all animals in DLS (left) and VS (right). Electrode tip positioning were superimposed on atlas planar sections at depth of −3.86 (DLS) and 6.82 (VS) from Bregma. Black marks the positioning of about 85% of the electrodes and dark and light gray mark the remaining 10 and 5%, respectively.

Figure 2

Neurons were classified based on their firing properties and waveform shapes. (A) Scatter plot of firing rate, cv, and VAR showing the separation of the recorded neurons into three groups categorized as: pMSNs, pTANs, and pFSIs. The inset below the 3D plot demonstrates how the valley amplitude and the valley to following peak amplitude were measured. (B) A 2D plot of VAR vs. firing rate. (C) ISI distributions of three representative neurons: pMSN (top), pTAN (middle) and pFSI (bottom) and the average waveforms of each cell type (D). An example of a single pTAN recorded continuously. (E) Histograms of the percent of pMSNs, pTANs, and pFSIs with different proportions of time in ISIs longer than 2 s.

Figure 3

Putative tonically active neurons in DLS and in VS exhibit movement-related activity. (A) Raster plots and their corresponding peri-event time histograms (PETHs) of a direction selective pTAN recorded in VS. Trials are presented top to bottom as they were presented during the session. Entering the center hole is marked in tan; beginning of the tone is marked in light blue; movement initiation is marked in green; and reward is marked in violet. Top panel: plot is aligned to the beginning of movement toward the left side; middle: plot is aligned to beginning of movement to the right side; bottom: plot is aligned to reward. (B) Percent of movement related and direction selective pTANs in DLS and VS. (C) Percent of direction selective pTANs in which the preferred direction was contralateral or ipsilateral to the recording site.

Figure 4

Firing patterns characteristics of pTANS in DLS and in VS. (A) Average, normalized population activity of direction selective DLS (top) and VS (bottom) pTANs during movement, separated into preferred and non-preferred directions. Error bars are standard error of means. (B) pTANs in DLS and in VS exhibit distinct direction selectivity patterns. On the left: selectivity patterns marking movement phases with significant difference between left and right activation. For example, the top row includes neurons which exhibited significant left and right firing differences during the middle and end of movement but not after movement initiation. On the right: the percent of pTANs in DLS (blue) and VS (red) assigned to each of the patterns. (C) Selectivity indices of direction selective pTANs in DLS and VS. Average values of SI are marked by rectangles. (D) Percent of trials in which movement direction was correctly predicted from the activity of single neurons, averaged over animals. Error bars are standard error of the means. (E) Percent of trials predicted correctly by the best neurons in each striatal region.