Maturation of GABAergic Inhibition Promotes Strengthening of Temporally Coherent Inputs among Convergent Pathways

Abstract

Spike-timing-dependent plasticity (STDP), a form of Hebbian plasticity, is inherently stabilizing. Whether and how GABAergic inhibition influences STDP is not well understood. Using a model neuron driven by converging inputs modifiable by STDP, we determined that a sufficient level of inhibition was critical to ensure that temporal coherence (correlation among presynaptic spike times) of synaptic inputs, rather than initial strength or number of inputs within a pathway, controlled postsynaptic spike timing. Inhibition exerted this effect by preferentially reducing synaptic efficacy, the ability of inputs to evoke postsynaptic action potentials, of the less coherent inputs. In visual cortical slices, inhibition potently reduced synaptic efficacy at ages during but not before the critical period of ocular dominance (OD) plasticity. Whole-cell recordings revealed that the amplitude of unitary IPSCs from parvalbumin positive (Pv+) interneurons to pyramidal neurons increased during the critical period, while the synaptic decay time-constant decreased. In addition, intrinsic properties of Pv+ interneurons matured, resulting in an increase in instantaneous firing rate. Our results suggest that maturation of inhibition in visual cortex ensures that the temporally coherent inputs (e.g. those from the open eye during monocular deprivation) control postsynaptic spike times of binocular neurons, a prerequisite for Hebbian mechanisms to induce OD plasticity.

Distinct maturation profiles of perisomatic and dendritic targeting GABAergic interneurons in the mouse primary visual cortex during the critical period of ocular dominance plasticity

“…This may reflect increased involvement of this source of inhibition in more mature cortical circuits. The developmental profile of PV cells was consistent with previous studies (Doischer et al 2008;Okaty et al 2009;Kuhlman et al 2010) and demonstrated the postnatal acquisition of fast-spiking characteristics (McCormick et al 1985).…”

“…Postnatal development of layer II/III pyramidal cells leads to lower input resistance (Luhmann and Prince 1991;Desai et al 2002;Kuhlman et al 2010) and hyperpolarized V M (Luhmann and Prince 1991;Desai et al 2002; M. S. Lazarus and Z. J. Huang, unpublished observations), which should reduce cell excitability. The substantial increase of excitability of SOM cells may reflect a stronger engagement of this type of inhibition in V1 circuits during the critical period.…”

“…Furthermore, mature PV cells are characterized by their "fast in and fast out" signal transmission (Jonas et al 2004) and thus are highly effective in converting the pattern of excitatory input into well-timed inhibitory output to the perisomatic region, thereby controlling the spiking pattern of innervated pyramidal neurons. PV fast-spiking interneurons therefore appear ideally suited to detect and transmit precise input spiking patterns in V1, a necessary step in the engagement of plasticity mechanisms (Huang and Di Cristo 2008;Hensch 2005), e.g., spike timing-dependent plasticity, which may already be in place at that time (Kuhlman et al 2010). Here, we have shown that the intrinsic and synaptic properties of V1 PV cells remain immature after eye opening but are significantly sharpened during the onset of OD plasticity.…”

Early- and Late-Born Parvalbumin Basket Cell Subpopulations Exhibiting Distinct Regulation and Roles in Learning

“…In addition, PV Basket cells inhibit each other reciprocally through perisomatic innervation and are dynamically coupled electrically through gap junctions (Bartos et al, 2007;Hu et al, 2014). As a result, PV Basket cells filter activation of principal neurons, and networks of PV Basket cells have major roles in regulating local ensemble activities, including theta and gamma oscillations (Fuchs et al, 2007;Cardin et al, 2009;Kuhlman et al, 2010;Isaacson and Scanziani, 2011;Lee et al, 2012;Hu et al, 2014). Synaptic regulation of PV Basket cells has been implicated in adult learning, and the maturation state of PV Basket cells has been implicated in critical period-type plasticity (Hensch et al, 1998;Hensch, 2005;Di Cristo et al, 2007;Southwell et al, 2010;Kuhlman et al, 2013;Wolff et al, 2014).…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…This process is experience dependent, that is it cannot begin before eye opening, after which the critical period for setting ocular dominance and visual acuity is started (Fagiolini and Hensch, 2000;Sugiyama et al, 2009). Pv-interneurons in the visual cortex mature in connections (e.g., forming perisomatic synapses on principal neurons) and intrinsic firing properties (e.g., fast spiking) by the end of the critical period, thus allowing the firm functional cortical connections for binocular visual acuity to be formed (Kuhlman et al, 2010). PNNs interact with receptors such as NgR1 (NoGo receptor) and leukocyte common antigene-related phosphatase (Akbik et al, 2013;Ye and Miao, 2013).…”