The conditioned emotional response evoked by contextual fear is modulated by lateral hypothalamus synaptic activity without the involvement of GABAA receptor activation

The Lateral Hypothalamic Area (LHA) modulates autonomic responses during defensive reactions. However, the role of the LHA in modulating behavioral and autonomic responses induced by contextual fear conditioning (CFC) remains unclear. To investigate the involvement of the LHA in these responses, we conducted a study using various reversible inhibitors in the LHA.

Prior to re-exposing the animals to the aversive context, we performed acute, reversible, specific, and non-specific inhibition using lidocaine (100nL), a nonselective synapse inhibitor (CoCl₂, 1 mM/100 nL), or a GABA_A receptor agonist (muscimol, 0.1, 1, and 10 nmol/100 nL) in rats. Unconditioned animals (not exposed to shocks) and conditioned animals (exposed to low- or high-intensity shocks during the conditioning session) exhibited a freezing response and increased autonomic activity (with increased mean arterial pressure and heart rate, while cutaneous temperature decreased) when reintroduced to the chamber. Local inhibition of LHA neurotransmission increased the behavioral response only in the conditioned group subjected to low-intensity shocks. However, unconditioned animals also showed increased autonomic responses. In contrast, inhibition via GABA_A receptor activation did not produce any effects.

In conclusion, our study provides insights into the complex role of LHA synaptic activity in fear conditioning responses, highlighting its involvement in modulating behavior and autonomic responses based on aversive intensity and indicating that GABA_A receptors are not involved in this process. Additionally, our findings emphasize that the LHA plays a significant role in modulating autonomic activity in both learned and innate threatening scenarios.