Role of pannexin 1 in the modulation of inhibitory synaptic plasticity in mouse hippocampus
Fecha
2022-03
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Facultad de Ciencias
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Facultad de Ciencias, Programa de Doctorado en Ciencias Mención en Neurociencia
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Doctora en Ciencias con Mención en Neurociencia. Universidad de Valparaíso. 2022.
Resumen
The interplay between excitatory and inhibitory activity is essential for neural circuit refinement and learning. A large variety of proteins modulate the efficacy of excitatory glutamatergic circuits. However, only in recent years, has been studied their impact on inhibitory GABAergic circuits. Recently it has been shown that Pannexin 1 (Panx1), a non-selective transmembrane channel that allows the passage of several ions and metabolites such as ATP, can regulate glutamatergic transmission, however, its functional role in GABAergic transmission is unknown. Using the patch- clamp technique, pharmacology, transgenic and wild-type mouse we studied the contribution of Panx1 on the GABAergic synaptic efficacy in CA1 pyramidal neurons (PyNs). Here, we report that blockage of Panx1 reduces the GABAergic synaptic transmission in the hippocampus. Specifically, we observed a decrease in the amplitude of evoked inhibitory postsynaptic currents (eIPSCs), a reduction in the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), and a decrease in GABA release onto CA1 PyNs. In addition, we show that the depression in GABAergic synaptic transmission induced by Panx1 blockage involves the activation of cannabinoid CB1 receptors which depressed GABA release via a presynaptic Ca2+-dependent downregulation of PKA signaling.
In conclusion, our results indicate that neuronal Panx1 is an important regulator of hippocampal GABAergic transmission suggesting it might play a role in brain functions and cognitive processes.
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PROCESOS COGNITIVOS, PLASTICIDAD NEURONAL, GABAergicos, HIPOCAMPO