RESUMO
Alterations in glutamatergic transmission onto developing GABAergic systems, in particular onto parvalbumin-positive (Pv(+)) fast-spiking interneurons, have been proposed as underlying causes of several neurodevelopmental disorders, including schizophrenia and autism. Excitatory glutamatergic transmission, through ionotropic and metabotropic glutamate receptors, is necessary for the correct postnatal development of the Pv(+) GABAergic network. We generated mutant mice in which the metabotropic glutamate receptor 5 (mGluR5) was specifically ablated from Pv(+) interneurons postnatally, and investigated the consequences of such a manipulation at the cellular, network and systems levels. Deletion of mGluR5 from Pv(+) interneurons resulted in reduced numbers of Pv(+) neurons and decreased inhibitory currents, as well as alterations in event-related potentials and brain oscillatory activity. These cellular and sensory changes translated into domain-specific memory deficits and increased compulsive-like behaviors, abnormal sensorimotor gating and altered responsiveness to stimulant agents. Our findings suggest a fundamental role for mGluR5 in the development of Pv(+) neurons and show that alterations in this system can produce broad-spectrum alterations in brain network activity and behavior that are relevant to neurodevelopmental disorders.
Assuntos
Interneurônios/metabolismo , Interneurônios/patologia , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/patologia , Parvalbuminas/metabolismo , Receptores de Ácido Caínico/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/patologia , Masculino , Camundongos , Camundongos Knockout , Receptores de Glutamato Metabotrópico/genéticaRESUMO
Phase-amplitude modulation is a form of cross frequency coupling where the phase of one frequency influences the amplitude of another higher frequency. It has been observed in neurophysiological recordings during sensory, motor, and cognitive tasks, as well as during general anesthesia. In this paper, we describe a novel beamforming procedure to improve estimation of phase-amplitude modulation. We apply this method to 64-channel EEG data recorded during propofol general anesthesia. The method improves the sensitivity of phase-amplitude analyses, and can be applied to a variety of multi-channel neuroscience data where phase-amplitude modulation is present.
