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.

No abstract

Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output.

The brain’s orienting response is a biologically primitive, yet critical cognitive function necessary for survival. Though based on a wide network of brain regions, the lateral prefrontal cortex and posterior hippocampus are thought to play essential roles. Indeed, damage to these regions results in abnormalities of the novelty P3 or P3a, an event-related potential (ERP) sign of the orienting response. Like other ubiquitous markers of orienting, such as the galvanic skin response, the P3a habituates when novel events are repeated. Here, we assessed habituation of the P3a in patients who had undergone unilateral anteromedial resection of the medial temporal lobe (AMTL), including the entire hippocampus, for relief of pharmacologically intractable epilepsy. Eight left- and 8 right-AMTL patients and 16 age- and education-matched controls heard frequent standard tones, infrequent targets (requiring reaction times) and equally infrequent, unique novel, environmental sounds. The novel sounds repeated 2 blocks after their first presentation. In controls, novel repetition engendered a reduction in P3a amplitude, but this was not the case in either left- or right-AMTL patients. We conclude that bilaterally intact hippocampi are necessary for the brain to appreciate that a repetition of a novel sound has occurred, perhaps due to disruptions in ipsilateral hippocampal-prefrontal pathways and/or between the left and right hippocampi.

The lateral preoptic-rostral lateral hypothalamic continuum (LPH) receives projections from the nucleus accumbens and is believed to be one route by which nucleus accumbens signaling affects motivated behaviors. While accumbens firing patterns are known to be modulated by fluctuating levels of cocaine, studies of the LPH's drug related firing are absent from the literature. The present study sought to electrophysiologically test whether drug-related tonic and slow-phasic patterns exist in the firing of LPH neurons during a free-access cocaine self-administration task. Results demonstrated that a majority of neurons in the LPH exhibited changes in both tonic and slow phasic firing rate during fluctuating drug levels. During the maintenance phase of self-administration, 69.6% of neurons exhibited at least a two-fold change in tonic firing rate when compared to their pre-drug firing rates. Moreover, 54.4% of LPH neurons demonstrated slow-phasic patterns, specifically ‘progressive reversal’ patterns, which have been shown to be related to pharmacological changes across the inter-infusion interval. Firing rate was correlated with calculated drug level in 58.7% of recorded cells. Typically, a negative correlation between drug level and firing rate was observed, with a majority of neurons showing decreases in firing during cocaine self-administration. A small percentage of LPH neurons also exhibited correlations between locomotor behavior and firing rate, however, correlations with drug level in these same neurons were always stronger. Thus, the relationship between LPH firing and locomotion is weak, at best. Overall, these findings suggest that a proportion of LPH neurons are sensitive to fluctuations in cocaine concentration and may contribute to neural activity that controls drug taking.