Ghrelin receptor impairs inhibitory neurotransmission in hippocampal neurons in a ghrelin independent manner

MARTÍNEZ DAMONTE V; RODRIGUEZ SILVIA S.; RAINGO JESICA

Cordoba

Congreso; XXXIII reunión anual de la SAN; 2018

Sociedad Argentina de Investigación en Neurociencias

GHSR is a G-protein coupled receptor that displays high constitutive activity, independent from its endogenous ligand, ghrelin, relying exclusively on GHSR expression levels. It is widely expressed in the nervous system, including regions with restricted ghrelin access, as the hippocampus, but the mechanisms underlying neuronal modulation by GHSR remain elusive. Our previous work demonstrated that presynaptic voltage-gated calcium channels (CaV2), which allow the calcium influx that triggers neurotransmitter release, are highly sensitive to GHSR constitutive activity. Our aim here was to study the impact of CaV2 modulation by GHSR on hippocampal neurotransmission. We performed electrophysiological recordings in hippocampal primary cultures from E16-18 wild type and GHSR-deficient mice after manipulating GHSR expression levels by lentiviral transduction. We found that GHSR constitutive activity impairs CaV2 currents, being CaV2.2 the most affected subtype. Moreover we found that GHSR constitutive activity decreases inhibitory but not excitatory post-synaptic currents, without affecting CaV2-independent forms of neurotransmitter releaseWe show that GHSR constitutive activity modulates inhibitory neurotransmission in hippocampal neurons through a presynaptic mechanism mediated mainly by CaV2.2 currents impairment that specifically affects GABA release. Our work provides insights in assessing the role of GHSR in neurotransmission and plasticity at hippocampal synapses.