Nucleus incertus ablation disrupted conspecific recognition and modified immediate early gene expression patterns in 'social brain' circuits of rats.

Social interaction involves neural activity in prefrontal cortex, septum, hippocampus, amygdala and hypothalamus. Notably, these areas all receive projections from the nucleus incertus (NI) in the pontine tegmentum. Therefore, we investigated the effect of excitotoxic lesions of NI neurons in adult male, Wistar rats on performance in a social discrimination test, and associated changes in immediate-early gene protein levels. NI was lesioned with quinolinic acid, and after recovery, rats underwent two trials in the 3-chamber test. In the first trial, NI-lesioned and sham-lesioned rats spent longer exploring a conspecific than an inanimate object. By contrast, in the second trial, NI-lesioned rats visited the familiar and novel conspecific chambers equally, whereas sham-lesioned rats spent longer engaging with the novel rat. Quantification of Fos- and Egr-1-immunoreactivity (IR) levels in brain areas implicated in social behaviour, revealed that social encounter and NI lesion produced complex, differential changes. For example, Egr-1-IR was broadly decreased in several amygdala nuclei in NI-lesioned rats relative to sham, but Fos-IR levels were unaltered. In hippocampus, NI-lesioned rats displayed decreased Fos-IR in CA2 and CA3, while Egr-1-IR was increased in the polymorphic dentate gyrus, CA1, CA2 and subiculum of NI-lesioned rats, relative to sham. Social encounter-related Egr-1-IR was also decreased in septum and anterior and lateral hypothalamus of NI-lesioned rats. Overall, these data suggest NI networks can modulate the activity of sensory, emotional and executive brain areas involved in social recognition, with a likely involvement of neuronal Egr-1 activation in amygdala, septum and hypothalamus, and Erg-1 inhibition in hippocampus.

The antero-posterior heterogeneity of the ventral tegmental area.

The ventral tegmental area (VTA) is a brain region processing salient sensory and emotional information, controlling motivated behaviors, natural or drug-related reward, reward-related learning, mood, and participating in their associated psychopathologies. Mostly studied for its dopamine neurons, the VTA also includes functionally important GABA and glutamate cell populations. Behavioral evidence supports the presence of functional differences between the anterior VTA (aVTA) and the posterior VTA (pVTA), which is the topic of this review. This antero-posterior heterogeneity concerns locomotor activity, conditioned place preference and intracranial self-administration, and can be seen in response to ethanol, acetaldehyde, salsolinol, opioids including morphine, cholinergic agonists including nicotine, cocaine, cannabinoids and after local manipulation of GABA and serotonin receptors. It has also been observed after viral-mediated manipulation of GluR1, phospholipase Cγ (PLCγ) and cAMP response element binding protein (CREB) expression, with impact on reward and aversion-related responses, on anxiety and depression-related behaviors and on pain sensitivity. In this review, the substrates potentially underlying these aVTA/pVTA differences are discussed, including the VTA sub-nuclei and the heterogeneity in connectivity, cell types and molecular characteristics. We also review the role of the tail of the VTA (tVTA), or rostromedial tegmental nucleus (RMTg), which may also participate to the observed antero-posterior heterogeneity of the VTA. This region, partly located within the pVTA, is an inhibitory control center for dopamine activity. It controls VTA and substantia nigra dopamine cells, thus exerting a major influence on basal ganglia functions. This review highlights the need for a more comprehensive analysis of VTA heterogeneity.