A key mechanism underlying sensory experience-dependent maturation of neocortical GABAergic circuits in vivo

Abstract

Mechanisms underlying experience-dependent refinement of cortical connections, especially GABAergic inhibitory circuits, are unknown. By using a line of mutant mice that lack activity-dependent BDNF expression (bdnf-KIV), we show that experience regulation of cortical GABAergic network is mediated by activity-driven BDNF expression. Levels of endogenous BDNF protein in the barrel cortex are strongly regulated by sensory inputs from whiskers. There is a severe alteration of excitation and inhibition balance in the barrel cortex of bdnf-KIV mice as a result of reduced inhibitory but not excitatory conductance. Within the inhibitory circuits, the mutant barrel cortex exhibits significantly reduced levels of GABA release only from the parvalbumin-expressing fast-spiking (FS) interneurons, but not other interneuron subtypes. Postnatal deprivation of sensory inputs markedly decreased perisomatic inhibition selectively from FS cells in wild-type but not bdnf-KIV mice. These results suggest that postnatal experience, through activity-driven BDNF expression, controls cortical development by regulating FS cellmediated perisomatic inhibition in vivo.neurotrophin | plasticity | brain derived neurotrophic factor

Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

“…PV interneuron deficits and GABAergic transmission also were observed in mutant barrel cortex (35). Here, we show that hippocampal GABAergic transmission and STDP are normal in BDNF-KIV mice.…”

Structural alterations in fast-spiking GABAergic interneurons in a model of posttraumatic neocortical epileptogenesis

“…Because of the known trophic effects of BDNF via TrkB receptors on interneuronal structure and function (Marty et al, 1996; McAllister et al, 1999); (Jin et al, 2003); (Rutherford et al, 1997); (Elmariah et al, 2004), and the possibility that the injury and deafferentation inherent in the UC model would decrease activity-driven BDNF expression (Jiao et al, 2011); (Lin et al, 2008); (Hong et al, 2008); (Sakata et al, 2009), we assessed effects of UC on BDNF-IR in layer V Pyr cells 7 days (15 cells from 3_sections/rat; 3 control and 3 UC rats) (Fig. 10) and 3 weeks after UC (20 cells from 3 sections from 3 control and 3 UC rats) (Fig.…”

Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders

“…One of these, promoter IV, is the major activity-dependent promoter active in the neocortex. Selective disruption of promoter IV (Jiao et al, 2011; Sakata et al, 2009) or of the ability of the activity dependent transcription factor CREB to bind to promoter IV (Hong et al, 2008) selectively reduces inhibitory, but not excitatory synaptic transmission. Synapses from parvalbumin-positive interneurons are selectively disrupted (Jiao et al, 2011).…”

“…Selective disruption of promoter IV (Jiao et al, 2011; Sakata et al, 2009) or of the ability of the activity dependent transcription factor CREB to bind to promoter IV (Hong et al, 2008) selectively reduces inhibitory, but not excitatory synaptic transmission. Synapses from parvalbumin-positive interneurons are selectively disrupted (Jiao et al, 2011). Presumably, it is this signaling pathway that permits the precise matching of PV + inhibitory to excitatory synaptic strength onto pyramidal cells, and which permits this balance to be adjusted following perturbations that alter sensory drive or pyramidal neuron activity (House et al, 2011; Xue et al, 2014).…”