CB1 receptor located in gabaergic neurons expressing somatostatin regulate synaptic transmission in the prefrontal cortex

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dc.contributor.advisorDirectora de Tesis: Chiu, Chiayu
dc.contributor.authorSanguinetti González, Nicole
dc.coverage.spatialValparaíso
dc.date.accessioned2024-08-07T17:12:50Z
dc.date.available2024-08-07T17:12:50Z
dc.date.issued2019
dc.description.abstractEndocannabinoids (eCBs) are potent modulators of synaptic function throughout the central nervous system (CNS). Alterations in the eCB system are observed in several neuropsychiatric disorders, including schizophrenia and attention deficit disorder, prompting the suggestion that eCBs modulate emotional and cognitive processes in associative areas such as the prefrontal cortex (PFC). However, the specific neural circuits and cell types participating in eCB-dependent signaling in the PFC have not been well elucidated. Given the importance of synaptic inhibition in shaping neural activity, we study the potential impact of eCBs at GABAergic synapses from a major population of dendrite- targeting interneurons that express somatostatin (SOM-INs) in the PFC. Using optogenetic tools to selectively activate SOM-INs in acute brain slices, we investigate whether GABA release from SOM-INs are regulated by eCB signaling through activation of its canonical type 1 cannabinoid receptor (CB1R). We found that inhibition onto cortical pyramidal cells evoked by optical stimulation of channelrhodopsin 2 (ChR2)-expressing SOM-INs are depressed by WIN 55,212-2, a potent agonist of CB1Rs, in control mice. Next, we generated mice lacking CB1Rs in SOM-INs (SOM-CB1R KO) and confirmed the absence of WIN-depression at these inhibitory synapses. We further assessed the impact of removing CB1Rs from SOM-INs on inhibitory synaptic transmission. Input-output curves of electrically stimulated inhibitory responses (eIPSCs) in layer 2/3 pyramidal neurons suggest an upregulation of dendritic inhibition in SOM-CB1R KO mice compared to littermate controls. In support of this interpretation, eIPSCs in SOM-CB1R KOs also showed stronger paired pulse depression compared to controls. Moreover, spontaneous inhibitory activity increased in frequency but not amplitude in SOM-CB1 KOs compared to control mice. Together, these results suggest an important contribution of eCBs to control GABAergic inhibition from SOM-INs. By targeting dendritic regions of pyramidal cells where excitatory synapses congregates, SOM-INs can profoundly modulate synaptic integration to influence principal cell output. Thus, through its effect on inhibition mediated by SOM-INs, the eCB system would be able to fine-tune information flow in the PFC from sources such as the thalamus, hippocampus and amygdala to shape associative cognitive processing.
dc.facultadFacultad de Ciencias
dc.identifier.urihttps://repositoriobibliotecas.uv.cl/handle/uvscl/14210
dc.language.isoen
dc.publisherUniversidad de Valparaíso
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subjectGABAergicos
dc.subjectSOMATOSTATINA
dc.subjectSINAPSIS
dc.titleCB1 receptor located in gabaergic neurons expressing somatostatin regulate synaptic transmission in the prefrontal cortex
dc.typeThesis
uv.catalogadorPJR CIEN
uv.colectionTesis
uv.departamentoFacultad de Ciencias. Programa de Magíster en Ciencias Biológicas Mención Neurociencia
uv.notageneralMagíster en Ciencias Biológicas Mención Neurociencias. Universidad de Valparaíso. 2019.

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