Serotonin 5-HT1A receptors modulate neural rhythms in prefrontal cortex and hippocampus and prefronto-hippocampal connectivity in alert mice

Theserotonergic system plays a crucial role in cognition and is a target of many psychiatric treatments. In particular, serotonin 5-HT1A receptors (5-HT1AR) in the prefrontal cortex and hippocampus play key roles in learning, memory, behavioral flexibility, and response inhibition. Here, we investigated how 5-HT1A receptors influence neural network dynamics in the prefrontal cortex and hippocampus and prefronto-hippocampal functional connectivity in alert mice. We found that pharmacological stimulation of 5-HT1AR with 8-OH-DPAT markedly reduces theta, beta, and high gamma oscillations in both areas and weakens prefronto-hippocampal phase synchronization at theta and beta frequencies. Pharmacological inhibition of 5-HT1A receptors with WAY-100635 reduces theta and high gamma oscillatory activity but increases beta and delta oscillations. It also weakens prefronto-hippocampal phase synchronization at theta frequencies. These results reveal that prefronto-hippocampal neurodynamics are highly sensitive to 5-HT1A manipulation and may be relevant for understanding the actions of psychiatric medication targeting the serotonergic system.