Exposure to hot and cold environments activates neurons projecting from the paraventricular thalamic nucleus to brain regions related to approach and avoidance behaviors.

Although cool- and warm-seeking behaviors for behavioral thermoregulation are considered to be appetitive/approach and aversive/avoidance behaviors, the neuronal circuits mediating such behaviors remain to be elucidated. A growing body of evidence suggests that the paraventricular thalamic nucleus (PVT) is a key brain region in a neuronal circuit that mediates appetitive/approach and aversive/avoidance behaviors. In this study, to elucidate the neuronal circuits mediating behavioral thermoregulatory responses, we examined whether neuronal pathways from the PVT to the nucleus accumbens (NAc), bed nucleus of the stria terminalis (BNST), and central nucleus of the amygdala (CeA), which are brain regions implicated in mediating appetitive/approach and aversive/avoidance behaviors, are activated during exposure to hot (38°C) and cold (8°C) environments using c-Fos immunostaining and retrograde tracing. Our results showed activation of neuronal pathways from the PVT to the NAc, BNST, and CeA during exposure to hot and cold environments, suggesting that activation of these pathways may be involved in avoidance behaviors from hot and cold environments for behavioral thermoregulation.

Chronic cocaine exposure induces noradrenergic modulation of inhibitory synaptic transmission to cholinergic neurons of the laterodorsal tegmental nucleus.

The laterodorsal tegmental nucleus (LDT), which sends cholinergic efferent connections to dopaminergic (DA) neurons in the ventral tegmental area (VTA), plays a critical role in the development of addictive behavior and the reinstatement of cocaine-seeking behavior. Although repeated cocaine exposure elicits plastic changes in excitatory synaptic transmission and intrinsic membrane excitability in LDT cholinergic neurons, it remains unclear whether inhibitory synaptic transmission is modulated by cocaine exposure. The LDT receives fibers containing noradrenaline (NA), a neurotransmitter whose extracellular levels increase with cocaine exposure. Therefore, it is hypothesized that repeated cocaine exposure induces plastic changes in LDT cholinergic neurons via NA. Ex vivo electrophysiological recordings in LDT cholinergic neurons were obtained from rats repeatedly exposed to cocaine. Bath-application of NA induced similar levels of hyperpolarization in both saline- and cocaine-treated neurons. However, NA attenuated the amplitude of inhibitory postsynaptic currents (IPSCs) in cocaine- but not saline-treated neurons through α2 adrenoceptors. This NA-induced IPSC attenuation was observed in the presence of strychnine, but not gabazine, indicating that NA modulated GABAergic but not glycinergic neurotransmission. NA increased the paired-pulse ratios of evoked IPSCs and decreased the frequencies of miniature IPSCs (mIPSCs) without affecting their amplitudes, suggesting a presynaptic mechanism. These findings suggest that repeated cocaine exposure induces neuroplasticity in GABAergic synaptic transmission onto LDT cholinergic neurons by probably modulating presynaptic α2 adrenoceptors. This potentially increases the activity of LDT cholinergic neurons, which might contribute to the development of addictive behavior by enhancing VTA DA neuronal activity.