Nicotinic regulation of experience-dependent plasticity in visual cortex

Abstract

While the cholinergic neuromodulatory system and muscarinic acetylcholine receptors (AChRs) have been appreciated as permissive factors for developmental critical period plasticity in visual cortex, it was unknown why plasticity becomes limited after the critical period even in the presence of massive cholinergic projections to visual cortex. In this review we highlighted the recent progresses that started to shed light on the role of the nicotinic cholinergic neuromodulatory signaling on limiting juvenile form of plasticity in the adult brain. We introduce the Lynx family of proteins and Lynx1 as its representative, as endogenous proteins structurally similar to α-bungarotoxin with the ability to bind and modulate nAChRs to effectively regulate functional and structural plasticity. Remarkably, Lynx family members are expressed in distinct subpopulations of GABAergic interneurons, placing them in unique positions to potentially regulate the convergence of GABAergic and nicotinic neuromodulatory systems to regulate plasticity. Continuing studies of the potentially differential roles of Lynx family of proteins may further our understanding of the fundamentals of molecular and cell type-specific mechanisms of plasticity that we may be able to harness through nicotinic cholinergic signaling.

Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on Place Navigation

“…The most common nAChR subtypes found in the brain are α7 and α4β2 receptors. Located at both pre- and postsynaptic sites, they play a pivotal role in various processes, such as learning and cognition ( 15 ), decision-making ( 9 ), and regulation of the postnatal development of the visual cortex ( 16 ). Thus, nicotinic ACh receptors constituted of specific subunits appear to be suitable pharmacological target for cognitive enhancement.…”

Mesoscopic Mapping of Stimulus-Selective Response Plasticity in the Visual Pathways Modulated by the Cholinergic System

“…Plasticity has to be reactivated in adults, specifically by manipulating the excitatory-inhibitory cortical balance via neuromodulation or by eliciting the long-term potentiation of the synapse strength. Also, neuronal plasticity could be reactivated via expression of plasticity factors that enhance plasticity, e.g., Lypd6 (Darvas et al, 2009 ; Sadahiro et al, 2016 ), or that structurize neuronal connectivity, such as the tissue plasminogen protein tPa (Mataga et al, 2002 ), and the synaptic proteins GAP43 (Han et al, 2013 ) or PSD95 (Kim and Sheng, 2004 ).…”

Lynx Prototoxins: Roles of Endogenous Mammalian Neurotoxin-Like Proteins in Modulating Nicotinic Acetylcholine Receptor Function to Influence Complex Biological Processes

“…Due to the experience and nAChR-dependent plasticity that occurs in the visual cortex (V1), it is a well-defined model for understanding the age-dependent molecular effects of lynx1 interactions with nAChRs. Lynx1 mRNA and protein levels increase in V1 at the end of the critical period, thereby decreasing ocular dominance plasticity (Morishita et al, 2010; Sadahiro et al, 2016). For example, the effects of lynx1 on ocular plasticity are demonstrated by an increase in responsiveness in the visual cortex in adult lynx1-null mutant KO mice during arousal, and by the discovery of a juvenile form of plasticity mediated by an interaction between lynx1 and tissue plasminogen activator (Morishita et al, 2010; Bukhari et al, 2015).…”