Rapid synaptic and gamma rhythm signature of mouse critical period plasticity

Published versio

Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity

Heightened neural excitability in infancy and childhood results in increased susceptibility to seizures. Such early-life seizures are associated with language deficits and autism that can result from aberrant development of the auditory cortex. Here, we show that early-life seizures disrupt a critical period (CP) for tonotopic map plasticity in primary auditory cortex (A1). We show that this CP is characterized by a prevalence of “silent,” NMDA-receptor (NMDAR)-only, glutamate receptor synapses in auditory cortex that become “unsilenced” due to activity-dependent AMPA receptor (AMPAR) insertion. Induction of seizures prior to this CP occludes tonotopic map plasticity by prematurely unsilencing NMDAR-only synapses. Further, brief treatment with the AMPAR antagonist NBQX following seizures, prior to the CP, pre

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry

Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons.

BACKGROUND: Oxidative stress and the specific impairment of perisomatic gamma-aminobutyric acid circuits are hallmarks of the schizophrenic brain and its animal models. Proper maturation of these fast-spiking inhibitory interneurons normally defines critical periods of experience-dependent cortical plasticity. METHODS: Here, we linked these processes by genetically inducing a redox dysregulation restricted to such parvalbumin-positive cells and examined the impact on critical period plasticity using the visual system as a model (3-6 mice/group). RESULTS: Oxidative stress was accompanied by a significant loss of perineuronal nets, which normally enwrap mature fast-spiking cells to limit adult plasticity. Accordingly, the neocortex remained plastic even beyond the peak of its natural critical period. These effects were not seen when redox dysregulation was targeted in excitatory principal cells. CONCLUSIONS: A cell-specific regulation of redox state thus balances plasticity and stability of cortical networks. Mistimed developmental trajectories of brain plasticity may underlie, in part, the pathophysiology of mental illness. Such prolonged developmental plasticity may, in turn, offer a therapeutic opportunity for cognitive interventions targeting brain plasticity in schizophrenia

Commentary: Microbial panaceas: does development have the answer? – reflections on Cowan, Dinan, & Cryan (2020)

Is the microbiome a promising adjunct, a potential panacea, or a distraction from feasible treatments for neurodevelopmental disorders? Taking a developmental approach may get us closer to understanding the data and give us pause in trying to translate this nascent field to the clinic right now