Major Effects of Sensory Experiences on the Neocortical Inhibitory Circuits

Abstract

During postnatal development, sensory experiences play critical roles in the refinement of cortical connections. However, both the process of postnatal experience-dependent maturation of neocortical inhibitory networks and its underlying mechanisms remain elusive. Here, we examined the differential properties of intracortical inhibitory networks of layer IV in "sensory-spared" and "sensorydeprived" cortices of glutamate acid decarboxylase 67 (GAD67)-green fluorescent protein (GFP) (⌬neo) and wild-type mouse. Our results showed that row D whisker trimming (WT) begun at postnatal day 7 (P7), but not after P15, induced a robust reduction of parvalbumin (PV) expression, measured by the PV/GFP ratio and PV cell densities, in the deprived barrels. WT also induced a robust reduction in the number of inhibitory perisomatic varicosities and synaptic GAD65/67 immunoreactivities in spiny neurons of the deprived barrels. Although the GAD65/67 expressions in interneurons were also downregulated in the deprived barrels, the GFP expression remained unchanged. Patch-clamp recording from spiny cells showed a 1.5-fold reduction of intracortical evoked IPSCs (eIPSCs) in deprived versus spared cortices. The reduction in eIPSCs occurred via changes in presynaptic properties and unitary IPSC amplitudes. Miniature IPSCs showed subtle but significant differences between the two experimental conditions. In addition, properties of the IPSCs in deprived barrels resemble those of IPSCs recorded in immature brains (P7). Together, these results suggest that the properties of local intracortical inhibitory networks are modified by sensory experiences. Perisomatic inhibition mediated by PV-positive basket cells is pruned by sensory deprivation.

α4* Nicotinic Acetylcholine Receptors Modulate Experience-Based Cortical Depression in the Adult Mouse Somatosensory Cortex

“…neurons and their perisomatic inhibitory boutons in layer 4 (Jiao et al, 2006). Further, whole-cell recordings of action potential firing properties and ion channel conductances in these cells indicated a net reduction in their intrinsic excitability (Sun, 2009).…”

“…There have been several recent studies showing that certain GABAergic neurons in layer 4 are very sensitive to changes in whisker experience (Jiao et al, 2006;Lee et al, 2007;P. Li et al, 2009).…”

“…Although it is certain that cortical depression takes place, the molecular mechanisms that mediate this form of plasticity are not well understood, especially for adult animals that are less well studied. Thus far, mechanistic studies conducted primarily in young animals have implicated glutamate (Rema et al, 1998;Takahashi et al, 2003;Clem et al, 2008;Wright et al, 2008;Dachtler et al, 2011) and cannabinoid (L. ) receptor signaling in experience-based cortical depression. This leaves open the possibility that other modulators of synaptic signaling, perhaps acting through inhibitory circuits which have recently been implicated in visual (Yazaki-Sugiyama et al, 2009) and barrel cortex plasticity (Jiao et al, 2006;Sun, 2009) may be involved.…”

GABA and neuroligin signaling: linking synaptic activity and adhesion in inhibitory synapse development

“…For example, the maturation of inhibitory innervation [3,4] and transmission [4,6] proceeds well into postnatal weeks and is regulated by sensory experience [3,6,31]. Interestingly, the maturation of many features of interneuron axonal arbors and inhibitory synapses can be recapitulated in cortical organotypic cultures [32] and is strongly regulated by neuronal activity [3,33].…”

“…GABAergic neurons are generated during mid-embryonic stages and influence many aspects of early neural development. The subsequent maturation of GABAergic synapses and innervation patterns into a potent inhibitory network is often a protracted process, extending well into postnatal life, and is regulated by neural activity and experience [3][4][5][6]. Such activity-dependent development of inhibitory synapses and innervation patterns is a major component of neural circuit assembly, yet the underlying cellular and molecular mechanisms are poorly understood.…”