Electrophysiological evidence of alterations to the nucleus accumbens and dorsolateral striatum during chronic cocaine self‐administration

Abstract

As drug use becomes chronic, aberrant striatal processing contributes to the development of perseverative drug-taking behaviors. Two particular portions of the striatum, the nucleus accumbens (NAc) and the dorsolateral striatum (DLS), are known to undergo neurobiological changes from acute to chronic drug use. However, little is known about the exact progression of changes in functional striatal processing as drug intake persists. We sampled single-unit activity in the NAc and DLS throughout 24 daily sessions of chronic, long-access cocaine self-administration and longitudinally tracked firing rates (FR) specifically during the operant response: an upward vertical head movement. A total of 103 neurons were held longitudinally and immunohistochemically localized to either NAc Medial Shell (n=29), NAc Core (n=30), or DLS (n=54). We modeled changes representative of each category as a whole. Results demonstrated that FRs of DLS Head Movement neurons were significantly increased relative to baseline during all sessions, while FRs of DLS Uncategorized neurons were significantly reduced relative to baseline during all sessions. NAc Shell neurons’ FRs were also significantly decreased relative to baseline during all sessions while FRs of NAc Core neurons were reduced relative to baseline only during training days 1-18 but were not significantly reduced on the remaining sessions (19-24). The data suggest that all striatal subregions show changes in FR during the operant response relative to baseline, but longitudinal changes in response firing patterns were observed only in the NAc Core, suggesting that this region is uniquely susceptible to plastic changes induced by abused drugs.

Homogeneous processing in the striatal direct and indirect pathways: single body part sensitive type IIb neurons may express either dopamine receptor D1 or D2

“…The present study used D1‐Cre and D2‐Cre mice, which are well categorized and highly representative of endogenous D1 and D2 neurons in the direct and indirect pathways (Gerfen et al ., ). We were able to unambiguously identify those neurons by their response to a brief 5 ms light pulse, and we are confident in our ability to record just a single neuron on any given wire across multiple recording sessions (Coffey et al ., ). We chose a conservative identification procedure with a short light pulse to ensure that the neurons classified as D1 and D2 MSNs were in fact directly sensitive to the light stimulation and not to secondary stimulation (e.g., through multisynaptic activation).…”

“…This is true for both the body examination and the optogenetic identification. Statistical analysis of this technique has shown that the waveforms we record on a single wire are significantly more likely to belong to a single neuron, than to two or more neurons (Coffey et al, 2015).…”

“…Signals were amplified and filtered (450 Hz to 10 kHz; roll off À1.5 dB/octave at 1 kHz and À6 dB/octave at 11 kHz), and digitized (50 kHz sampling frequency per wire) for off-line analysis (DataWave Technologies, Loveland, CO, USA). Every neuron was cluster cut off-line using strict procedures developed in our laboratory over 30 years (West et al, 1990;Carelli & West, 1991;Coffey et al, 2015). Waveform parameters were used to isolate single units from each recording, and autocorrelograms from each neuron's sorted spike times ensured that only a single neuron existed in each wire's recording.…”

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

“…Although the extent to which these mesoaccumbens DA-glutamate fibers participate in the neurobiology of drugs of abuse remains to be determined, we speculate that these axons may participate in the regulation of neuronal activity in cocaine self-administration. Specifically, electrophysiological recordings have shown that nAcc neurons exhibit rapid phasic firing patterns to related cues and actions to obtain the drug (Peoples et al, 1998; Ghitza et al, 2003, 2004, 2006; Fabbricatore et al, 2009, 2010; Coffey and Barker et al, 2015). The nAcc neurons also exhibit slow-phasic and tonic changes in firing rate that correlate with the pharmacological effects of cocaine, and do not correlate with the rapid phasic firing patterns (Fabbricatore et al, 2010).…”

Mesencephalic dopamine neurons interfacing the shell of nucleus accumbens and the dorsolateral striatum in the rat

“…In an initial study by Belin and Everitt (), using intrastriatal disconnection procedures, it was shown that interactions between ventral and dorsal areas in the striatum, mediated by dopamine, are crucial in the development of habitual cocaine‐seeking. These findings have been confirmed and extended in the context of addiction studies in more recent years, not only behaviorally but also using neurophysiological and neurochemical approaches (Adermark et al, ; Burton, Nakamura, & Roesch, ; Coffey et al, ; Keramati & Gutkin, ; Saddoris, Wang, Sugam, & Carelli, ; Willuhn, Burgeno, Everitt, & Phillips, ; Willuhn, Burgeno, Groblewski, & Phillips, ). Recent studies also show “spiraling” between the Acb‐s and Acb‐c in the context of behavioral actions and the transition from impulse control disorders into compulsive disorders (e.g., Besson et al, ; Diergaarde et al, ).…”