The Role of PV Neurons in Cortical Plasticity During Development of Mouse Visual Cortex

Understanding plasticity and learning has been a fundamental question of neuroscience for decades. The visual cortex is a classical system for studying plasticity specifically using the paradigm of ocular dominance plasticity (ODP) in which it is seen that brief periods of monocular deprivation (MD) as short as three days can cause changes in the relative responsiveness of excitatory neurons to stimulation of both eyes. Prior to these shifts in responsiveness of excitatory neurons, monocular deprivation causes a rapid reduction of firing rates in parvalbumin-expressing (PV) inhibitory neurons which is causally linked to the reorganization of excitatory networks following the perturbation. Converging evidence suggests that deprivation, not an imbalance between eye inputs triggers the rapid plasticity in PV neurons. This has not been directly tested in vivo, however. Using two-photon guided cell-attached recording we examined the impact of closing both eyes for 24 hours on PV neuron response properties in primary visual cortex of mouse. We found that binocular deprivation causes a 30% reduction in stimulus-induced mean evoked firing rate, similar to the decrease in PV neuron firing seen following 24 hours of monocular deprivation. This rapidly induced decrease in stimulus-induced mean evoked firing of PV neurons is specific to the critical period as it is not seen in post critical period aged mice. Whereas stimulus-induced mean evoked firing rate of PV neurons changes under perturbation back towards immature firing rates for PV neurons, other simultaneously developed properties, namely tuning properties do not significantly revert following deprivation. Unlike evoked mean firing rate, measurements of trial-to-trial variability revealed that stimulus-induced decreases in variability are significantly dampened by deprivation during both the critical period and the post critical period. These data establish that open-eye inputs are not required to drive deprivation-induced weakening of PV neuron evoked activity and that aspects of PV neuron response properties are malleable throughout life. This paradigm of binocular deprivation, although not useful for eliciting ODP (Frenkel & Bear, 2004), can still elicit the same effects on PV neurons as monocular deprivation, namely the 30% decrease in stimulus-evoked firing rate. Binocular deprivation is therefore a useful paradigm for the identification of molecular mechanisms that couple visual experience to postnatal regulation of PV neuron firing rate without complications such as inputs of callosal projections which can innervate primary visual cortex (Métin, Godement, & Imbert, 1988). We used this paradigm of 24 hours binocular deprivation to test the necessity of ErbB4 for the development and regulation of PV neuron firing. Indeed we found that ErbB4 is necessary for PV neurons to develop their normal stimulus-evoked firing rate. In addition, PV neurons lacking ErbB4 lose their ability to decrease their responses following deprivation. This decreased inhibition from PV neurons lacking ErbB4 is especially interesting since ERBB4 is a schizophrenia risk factor and schizophrenics have been found to have a deficit of inhibition within primary visual cortex (Yoon et al., 2009, 2010).