Advances in understanding visual cortex plasticity

Abstract

Visual cortical plasticity can be either rapid, occurring in response to abrupt changes in neural activity, or slow, occurring over days as a homeostatic process for adapting neuronal responsiveness. Recent advances have shown that the magnitude and polarity of rapid synaptic modifications are regulated by neuromodulators, while homeostatic modifications can occur through regulation of cytokine actions or N-methyl-d-aspartate (NMDA) receptor subunit composition. Synaptic and homeostatic plasticity together produce the normal physiological response to monocular impairments. In vivo studies have now overturned the dogma that robust plasticity is limited to an early critical period. Indeed, rapid physiological plasticity in the adult can be enabled by prior, experience-driven anatomical rearrangements or through pharmacological manipulations of the epigenome.

Figure 1. Neuromodulators direct the valence of synaptic plasticity through distinct signaling pathways

mAChR or α₁AR stimulation induces LTD through a PLC-dependant cascade, whereas mAChR or βAR activation of AC induces LTP. Enhancement of NMDAR currents by histamine augments LTP, possibly through increasing intracellular calcium levels. These observations suggest that activation of specific signaling pathways through discrete neuromodulator receptor subtypes dictates the direction of plasticity induced in visual cortex. AC: Adenylyl cyclase; ACh: Acetylcholine; α₁AR: alpha adrenergic receptor; βAR: beta adrenergic receptor; LTD: Long-term depression; LTP: Long-term potentiation; mAChR: Muscarinic acetylcholine receptor; NMDAR: N-methyl d-aspartate receptor; PLC: Phospholipase C.

Figure 2. Epigenetic remodeling of chromatin can enable ocular dominance plasticity through an ERK-mediated cascade

Visual experience (light) can activate ERK and its downstream neural targets, MSK and CREB. CREB-mediated transcription is normally modest, due to a tight chromatin conformation. A histone remodeling complex can open the chromatin conformation through phosphorylation and acetylation of histone H3, thereby increasing the rate of CREB-mediated transcription of plasticity genes. Activation of plasticity gene expression contributes to the ocular dominance plasticity in the visual cortex. LGN: lateral geniculate nucleus; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; MSK: mitogen-and stress-activated kinase; CREB: cAMP-response element binding protein; HRC: histone remodeling complex; P: phospho group; Ac: acetyl group; H: histone octamer.