Growth Hormone Secretagogue Receptor type 1a (GHSR1a) constitutive activity impairs voltage-gated calcium channels (CaV)- dependent inhibitory neurotransmission in hippocampal neurons

MUSTAFÁ EMILIO ROMÁN,; PERELLO MARIO; MARTÍNEZ DAMONTE, VALENTINA; RODRIGUEZ SILVIA S.; CORDISCO G. SANTIAGO; RAINGO, JESICA

Buenos Aires

Congreso; II FALAN Congress 2016; 2016

FALAN

GHSR1a is a G-protein coupled receptor highly expressed inseveral regions of the central nervous system both pre- andpost-synaptically. In the hippocampus, it has been descriptedthat ghrelin enhances excitatory neurotransmission. How itmodulates neuronal activity remains largely unexploredbut multiple mechanisms seem to be implicated. GHSR1adisplays both ghrelin-evoked, that depends on ghrelinbinding, and constitutive activity, which relies only onGHSR1a expression levels. Presynaptic CaV2 are essentialfor transducing action potentials into calcium influx tothe pre-synaptic terminal which triggers neurotransmitterrelease. We have found that CaV2 are efficiently inhibitedby GHSR1a constitutive and ghrelin-evoked activity inthe hippocampus. Thus, we propose that GHSR1a may beenriched in GABAergic neurons in the hippocampus in orderto impair GABAergic but not glutamatergic transmission.To evaluate this, we first recorded CaV2 total currents inmature (>12div) hippocampal cultured neurons from Gad2-tomato mice -transgenic mice that express red fluorescenttomato in gabaergic neurons- and found that tomatopositiveneurons display smaller CaV2 currents. Then, weevaluated CaV-dependent neurotransmission recordingexcitatory and inhibitory post synaptic currents usingdifferent strategies to modulate GHSR1a expression levelsin hippocampal cultured neurons and found an impairmentin GABAergic neurotransmission but no differences inglutamatergic transmission.