A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex

Abstract

Early sensory experience instructs the maturation of neural circuitry in cortex 1,2. This has been extensively studied in the primary visual cortex where loss of vision to one eye permanently degrades cortical responsiveness to that eye 3,4, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process 4-6, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following 24 hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates following monocular deprivation results from a rapid, though transient reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV cell evoked responses following monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmaco-genetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of L2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ocular dominance plasticity.

Deprivation-Induced Strengthening of Presynaptic and Postsynaptic Inhibitory Transmission in Layer 4 of Visual Cortex during the Critical Period

“…6 A, B), consistent with previous reports (Kullmann et al, 2005;Luscher et al, 2011). We first analyzed the axosomatic (presynaptic vs postsynaptic) distribution of goldlabeled ␥2-subunits at identified FS3 SP synapses.…”

“…Two recent papers (Hengen et al, 2013;Kuhlman et al, 2013) provide evidence that a rapid drop in FS activity after 1 d of MD, followed by a homeostatic rebound in FS activity by day 2 of MD, may gate the initial stages of CP plasticity in V1m and V1b. Coupled with the observation that FS plasticity changes sign (Ϫ to ϩ) at the opening of the CP Lefort et al, 2013), these data raise the possibility that potentiation at this synapse contributes to the gating of CP plasticity within L4.…”

Progressive maturation of silent synapses governs the duration of a critical period

“…During these refinements, in experience-dependent processes, synapses will be either stabilized (10) or pruned (11,12). Our model does not exclude an essential contribution of the inhibitory network in regulating critical period plasticity (15,16,67). Because thresholds for Hebbian plasticity are sculpted by inhibitory neurotransmission (68), it is very likely that a PSD-95-governed synaptic plasticity mechanism in silent synapse maturation acts in concert with the inhibitory circuitry to refine cortical networks during CPs.…”

“…In contrast, only permissive mechanisms have been shown to terminate CPs. Among these, the developmental increase of local inhibition appears to be the dominating mechanism to regulate cortical plasticity and CPs (15)(16)(17). Additionally, extracellular matrix remodeling is involved, as well as receptors of immune signaling, such as paired Ig-like receptor B (PirB), or axon pathfinding, such as Nogo (18)(19)(20)(21).…”

Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions

“…Reducing the levels of inhibition onto excitatory neurons is consistently observed following loss of input in cortex [10,[22][23][24][25][26][27] and has been hypothesized to be a first step in circuit reorganization following input loss [28]. Changes in inhibition can occur via a reduction in the number [12,22,24,26,27,[29][30][31][32][33] or strength of inhibitory synapses onto excitatory cells [33], as well as a reduction in the firing rate of the inhibitory neurons following deprivation either temporarily during development [11,34] or for longer time courses in adulthood [29].…”