RESUMEN
Monocular deprivation (MD) causes an initial decrease in synaptic responses to the deprived eye in juvenile mouse primary visual cortex (V1) through Hebbian long-term depression (LTD). This is followed by a homeostatic increase, which has been attributed either to synaptic scaling or to a slide threshold for Hebbian long-term potentiation (LTP) rather than scaling. We therefore asked in mice of all sexes whether the homeostatic increase during MD requires GluN2B-containing NMDA receptor activity, which is required to slide the plasticity threshold but not for synaptic scaling. Selective GluN2B blockade from 2-6â d after monocular lid suture prevented the homeostatic increase in miniature excitatory postsynaptic current (mEPSC) amplitude in monocular V1 of acute slices and prevented the increase in visually evoked responses in binocular V1 in vivo. The decrease in mEPSC amplitude and visually evoked responses during the first 2â d of MD also required GluN2B activity. Together, these results support the idea that GluN2B-containing NMDA receptors first play a role in LTD immediately following eye closure and then promote homeostasis during prolonged MD by sliding the plasticity threshold in favor of LTP.
Asunto(s)
Predominio Ocular , Potenciales Postsinápticos Excitadores , Ratones Endogámicos C57BL , Plasticidad Neuronal , Receptores de N-Metil-D-Aspartato , Animales , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Ratones , Masculino , Predominio Ocular/fisiología , Femenino , Plasticidad Neuronal/fisiología , Plasticidad Neuronal/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Evocados Visuales/fisiología , Corteza Visual/fisiología , Corteza Visual/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Privación Sensorial/fisiología , Potenciación a Largo Plazo/fisiología , Potenciación a Largo Plazo/efectos de los fármacos , Depresión Sináptica a Largo Plazo/fisiología , Depresión Sináptica a Largo Plazo/efectos de los fármacos , Estimulación Luminosa/métodosRESUMEN
Disinhibition is an obligatory initial step in the remodeling of cortical circuits by sensory experience. Our investigation on disinhibitory mechanisms in the classical model of ocular dominance plasticity uncovered an unexpected form of experience-dependent circuit plasticity. In the layer 2/3 of mouse visual cortex, monocular deprivation triggers a complete, "all-or-none," elimination of connections from pyramidal cells onto nearby parvalbumin-positive interneurons (PyrâPV). This binary form of circuit plasticity is unique, as it is transient, local, and discrete. It lasts only 1 d, and it does not manifest as widespread changes in synaptic strength; rather, only about half of local connections are lost, and the remaining ones are not affected in strength. Mechanistically, the deprivation-induced loss of PyrâPV is contingent on a reduction of the protein neuropentraxin2. Functionally, the loss of PyrâPV is absolutely necessary for ocular dominance plasticity, a canonical model of deprivation-induced model of cortical remodeling. We surmise, therefore, that this all-or-none loss of local PyrâPV circuitry gates experience-dependent cortical plasticity.
Asunto(s)
Predominio Ocular , Interneuronas/fisiología , Inhibición Neural , Plasticidad Neuronal , Parvalbúminas/metabolismo , Células Piramidales/fisiología , Corteza Visual/fisiología , Animales , Proteína C-Reactiva/metabolismo , Interneuronas/citología , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo , Células Piramidales/citología , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
A balance between synaptic excitation and inhibition (E/I balance) maintained within a narrow window is widely regarded to be crucial for cortical processing. In line with this idea, the E/I balance is reportedly comparable across neighboring neurons, behavioral states, and developmental stages and altered in many neurological disorders. Motivated by these ideas, we examined whether synaptic inhibition changes over the 24-h day to compensate for the well-documented sleep-dependent changes in synaptic excitation. We found that, in pyramidal cells of visual and prefrontal cortices and hippocampal CA1, synaptic inhibition also changes over the 24-h light/dark cycle but, surprisingly, in the opposite direction of synaptic excitation. Inhibition is upregulated in the visual cortex during the light phase in a sleep-dependent manner. In the visual cortex, these changes in the E/I balance occurred in feedback, but not feedforward, circuits. These observations open new and interesting questions on the function and regulation of the E/I balance.
Asunto(s)
Ritmo Circadiano/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Potenciales Postsinápticos Inhibidores/fisiología , Red Nerviosa/fisiología , Corteza Visual/fisiología , Vías Visuales/fisiología , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Red Nerviosa/citología , Inhibición Neural/fisiología , Técnicas de Cultivo de Órganos , Células Piramidales/fisiología , Corteza Visual/citología , Vías Visuales/citologíaRESUMEN
Models of firing rate homeostasis such as synaptic scaling and the sliding synaptic plasticity modification threshold predict that decreasing neuronal activity (for example, by sensory deprivation) will enhance synaptic function. Manipulations of cortical activity during two forms of visual deprivation, dark exposure (DE) and binocular lid suture, revealed that, contrary to expectations, spontaneous firing in conjunction with loss of visual input is necessary to lower the threshold for Hebbian plasticity and increase miniature excitatory postsynaptic current (mEPSC) amplitude. Blocking activation of GluN2B receptors, which are upregulated by DE, also prevented the increase in mEPSC amplitude, suggesting that DE potentiates mEPSCs primarily through a Hebbian mechanism, not through synaptic scaling. Nevertheless, NMDA-receptor-independent changes in mEPSC amplitude consistent with synaptic scaling could be induced by extreme reductions of activity. Therefore, two distinct mechanisms operate within different ranges of neuronal activity to homeostatically regulate synaptic strength.
Asunto(s)
Homeostasis/fisiología , Aprendizaje/fisiología , Plasticidad Neuronal/fisiología , Animales , Corteza Cerebral/fisiología , Oscuridad , Fenómenos Electrofisiológicos/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Moduladores del GABA/farmacología , Potenciación a Largo Plazo/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/fisiología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/fisiología , Privación SensorialRESUMEN
Rapid eye movement (REM) sleep is expressed at its highest levels during early life when the brain is rapidly developing. This suggests that REM sleep may play important roles in brain maturation and developmental plasticity. We investigated this possibility by examining the role of REM sleep in the regulation of plasticity-related proteins known to govern synaptic plasticity in vitro and in vivo. We combined immunohistochemistry with a classic model of experience-dependent plasticity in the developing brain known to be consolidated during sleep. We found that after the developing visual cortex is triggered to remodel, it is reactivated during REM sleep (as measured by FOS+ and ARC+ cells). This is accompanied by expression of several proteins implicated in synaptic long-term potentiation (PSD95 and phosphorylated (p), mTOR, cofilin, and CREB) across the different cortical layers. These changes did not occur in animals deprived of REM sleep, but were preserved in control animals that were instead awakened in non- (N) REM sleep. Collectively, these findings support a role for REM sleep in developmental brain plasticity.