The effect of cold exposure on glutamate transmission and neuronal excitability in the dorsomedial hypothalamus of male rats

Abstract

The dorsomedial hypothalamus (DMH) is a key brain region involved in thermoregulation, in part through activation of brown adipose tissue (BAT). The DMH functionally connects thermoreceptors in the skin to the sympathetic nervous system, which activates BAT and generates heat during cold exposure in mammals. While it is known that the DMH is essential for BAT activation, how cold exposure affects neuronal communication and excitability in the DMH remains unknown. We hypothesized that cold exposure affects synaptic communication in the DMH by altering glutamate transmission and neuronal excitability. To examine the potential effects of cold exposure on DMH synapses, we subjected young male Sprague Dawley rats to a two-hour cold exposure (2 - 4°C). To control for the effects of stress during cold exposure experiments, control (stress) experiments were performed with replicated procedures excluding the change in temperature. Patch clamp electrophysiology was then used to study glutamate signaling and excitability in the DMH of naive, cold-exposed, and stressed animals. We observed a decrease in baseline glutamate transmission in the DMH of cold exposed animals. This suggests that decreased glutamate transmission in the DMH may be involved in signaling cold temperatures and activating thermogenic processes regulated by the DMH. A long-term depression at glutamate synapses was observed in the DMH of both cold-exposed and stressed animals. As the long-term depression was also seen in stressed animals, who experienced similar environmental manipulation without a change in temperature, the observed depression was likely caused by stress and not cold exposure. There was no difference in action potential firing observed across naive, cold-exposed, and stressed animals, suggesting a two-hour cold exposure does not alter the excitability of DMH neurons. This study is the first to demonstrate that glutamate transmission is decreased in the DMH during cold exposure, representing a potential important neuronal mechanism involved in activating thermoregulatory strategies such as BAT thermogenesis.