In silico Hierarchical Clustering of Neuronal Populations in the Rat Ventral Tegmental Area Based on Extracellular Electrophysiological Properties.

The ventral tegmental area (VTA) is a heterogeneous brain region, containing different neuronal populations. During recordings, electrophysiological characteristics are classically used to distinguish the different populations. However, the VTA is also considered as a region harboring neurons with heterogeneous properties. In the present study, we aimed to classify VTA neurons using approaches, in an attempt to determine if homogeneous populations could be extracted. Thus, we recorded 291 VTA neurons during extracellular recordings in anesthetized rats. Initially, 22 neurons with high firing rates (>10 Hz) and short-lasting action potentials (AP) were considered as a separate subpopulation, in light of previous studies. To segregate the remaining 269 neurons, presumably dopaminergic (DA), we performed analyses, using a combination of different electrophysiological parameters. These parameters included: (1) firing rate; (2) firing rate coefficient of variation (CV); (3) percentage of spikes in a burst; (4) AP duration; (5) Δt duration (i.e., time from initiation of depolarization until end of repolarization); and (6) presence of a notched AP waveform. Unsupervised hierarchical clustering revealed two neuronal populations that differed in their bursting activities. The largest population presented low bursting activities (17.5%). Within non-high-firing neurons, a large heterogeneity was noted concerning AP characteristics. In conclusion, this analysis based on conventional electrophysiological criteria clustered two subpopulations of putative DA VTA neurons that are distinguishable by their firing patterns (firing rates and bursting activities) but not their AP properties

The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders

Ketamine is a non-competitive antagonist at the N-methyl-d-aspartate receptor. It has recently been found to have antidepressant effects and is a drug of abuse, suggesting it may have dopaminergic effects. To examine the effect of ketamine on the dopamine systems, we carried out a systematic review and meta-analysis of dopamine measures in the rodent, human and primate brain following acute and chronic ketamine administration relative to a drug-free baseline or control condition. Systematic search of PubMed and PsychInfo electronic databases yielded 40 original peer-reviewed studies. There were sufficient rodent studies of the acute effects of ketamine at sub-anaesthetic doses for meta-analysis. Acute ketamine administration in rodents is associated with significantly increased dopamine levels in the cortex (Hedge’s g= 1.33, P100 mg kg−1) of ketamine on dopamine levels ex vivo, although this remains to be tested in vivo. Findings in non-human primates and in human studies using positron emission tomography were not consistent. The studies reviewed here provide evidence that acute ketamine administration leads to dopamine release in the rodent brain. We discuss the inter-species variation in the ketamine induced dopamine release as well as the implications for understanding psychiatric disorders, in particular substance abuse, schizophrenia, and the potential antidepressant properties of ketamine, and comparisons with stimulants and other NMDA antagonists. Finally we identify future research needs