Potentiation of cortical inhibition by visual deprivation

Abstract

The fine-tuning of circuits in sensory cortex requires sensory experience during an early critical period. Visual deprivation during the critical period has catastrophic effects on visual function, including loss of visual responsiveness to the deprived eye, reduced visual acuity, and loss of tuning to many stimulus characteristics. These changes occur faster than the remodelling of thalamocortical axons, but the intracortical plasticity mechanisms that underlie them are incompletely understood. Long-term depression of excitatory intracortical synapses has been proposed as a general candidate mechanism for the loss of cortical responsiveness after visual deprivation. Alternatively (or in addition), the decreased ability of the deprived eye to activate cortical neurons could be due to enhanced intracortical inhibition. Here we show that visual deprivation leaves excitatory connections in layer 4 (the primary input layer to cortex) unaffected, but markedly potentiates inhibitory feedback between fast-spiking basket cells (FS cells) and star pyramidal neurons (star pyramids). Further, a previously undescribed form of long-term potentiation of inhibition (LTPi) could be induced at synapses from FS cells to star pyramids, and was occluded by previous visual deprivation. These data suggest that potentiation of inhibition is a major cellular mechanism underlying the deprivation-induced degradation of visual function, and that this form of LTPi is important in fine-tuning cortical circuitry in response to visual experience.

Delayed plasticity of inhibitory neurons in developing visual cortex

“…Intraocular TTX injection, lid suture, and dark rearing lead to a wide range of distinct changes in strengths of local connections among neurons in layers IV and II/III and in the intrinsic properties of those neurons in the monocular zone of the rat visual cortex before and at the beginning of the critical period (32,33). These changes do not account for the delayed plasticity of the visual responses of inhibitory neurons that we find in the binocular cortex in vivo.…”

“…Control (unmanipulated) animals were imaged at ages that spanned the critical period (postnatal days [25][26][27][28][29][30][31][32][33][34][35]. Imaging sessions began with intrinsic signal mapping of the binocular zone to locate the binocular portion of the primary visual cortex.…”

“…A purely Hebbian mechanism could never explain ocular dominance plasticity completely because it would make the deprived-eye responses disappear (30). Recent evidence indicates that the mechanism underlying nondeprived-eye response plasticity is distinct from these Hebbian changes (16,26,(31)(32)(33).…”

Wnt7a signaling promotes dendritic spine growth and synaptic strength through Ca 2+ /Calmodulin-dependent protein kinase II

“…The development of an appropriate balance of glutamatergic excitatory and GABAergic inhibitory synapses (E/I ratio) is essential for proper circuit function (1,2) because an imbalance in the E/I ratio can result in neurological disorders (3)(4)(5). Some synaptogenic factors regulate both excitatory and inhibitory synapses (6,7), whereas other synaptic organizers are more specific (8)(9)(10).…”

Developmental hearing loss eliminates long-term potentiation in the auditory cortex

“…During development, the magnitude of inhibitory long-term depression in the auditory brainstem declines after hearing onset (22). Visual deprivation has been shown to occlude LTP of inhibitory synaptic connections in the visual cortex (23), and chronic blockade of the NR2B subunit of the NMDA receptor eliminates excitatory synaptic LTP in adult mouse auditory cortex (24). Given the profound descending projection from auditory cortex to the amygdala, thalamus, and brainstem (25), any modification in synaptic plasticity within L5 of the ACx could influence both processing and learned responses (26,27).…”