The decline in synaptic GluN2B and rise in inhibitory neurotransmission determine the end of a critical period

Abstract

Neuronal plasticity is especially active in the young, during short windows of time termed critical periods, and loss of a critical period leads to functional limitations in the adults. The mechanism that governs the length of critical periods remains unknown. Here we show that levels of the NMDA receptor GluN2B subunit, which functions as a Ca2+ channel, declines in spinal cord synapses toward the end of the critical period for activity-dependent corticospinal synapse elimination. This period could be prolonged by blocking the decline of GluN2B, and after its termination the critical period could be reopened through upregulation of GluN2B. It is known that inhibitory neural activity increases with development in the CNS including the spinal cord. Suppression of the increasing inhibitory activity using low-dose strychnine also prolonged this critical period. During the strychnine-widened time window, Ca2+ influx through GluN2B channels returned to a level comparable to that seen during the critical period, though the level of GluN2B was slightly reduced. These findings indicate that loss of GluN2B subunits and the associated reduction in Ca2+ influx determines the end of the critical period in our in vitro CS system.

Hippocampal Synaptic Plasticity, Spatial Memory, and Neurotransmitter Receptor Expression Are Profoundly Altered by Gradual Loss of Hearing Ability

“…Strikingly, GluN2B expression was now significantly elevated in all cortical structures. The changes in the primary and parietal cortices are likely to reflect adaptive reorganization: A prolongation of the critical period results in a sustainment of the high expression of GluN2B subunits in the visual cortex ( Quinlan et al 1999 ), which is a typical characteristic of this period of cortical development ( Lee et al 2015 ; Isoo et al 2016 ). Treatment of rat pups with white noise results in a similar effect ( Hogsden and Dringenberg 2009a ).…”

“Can you Hear Me Now?” AMPA Receptor-Mediated Tonotopy Disruption by Early Life Seizures

“…The importance of critical period plasticity rests in prevention of developmental elimination of silent synapses. Thus, PTZ-induced seizures in this study or in strychnine-induced hyperexcitation (9) are effective in either closing down the window or keeping it open, again depending on the CNS system and timing of the impact.…”

“…Modifying events during critical periods may alter the system permanently; in other times, the system is just primed and the priming may be recalled later (8). Frequently, critical periods for various systems and functions in the CNS are associated with periods of heighten plasticity, a phenomenon that often (but not exclusively) involves NMDA receptor-mediated synaptic transmission modifiable by hyperexcitability (9). However, other plastic changes may be involved, such as plasticity/ development of GABA concentrations, chloride transporters, norepinephrine, or developmental loss of the GluN2B subunit of the NMDA receptor (9)(10)(11)(12).…”

Lung-injury depresses glutamatergic synaptic transmission in the nucleus tractus solitarii via discrete age-dependent mechanisms in neonatal rats

“…There is considerable evidence P11–15 represents a TP for breathing control in the rat-pup. Firstly, during this period excitatory and inhibitory transmission systems within several brainstem respiratory sites (including the nTS) undergo abrupt changes towards adult neuronal expression levels (Wong-Riley and Liu, 2008; Liu and Wong-Riley, 2010a, 2012a, 2013; Turner and Johnson, 2015; Bavis and MacFarlane, 2017), which are similar to TPs in other CNS sites (Kumar et al, 2002; Tyzio et al, 2007; Brill and Huguenard, 2008; Roberts et al, 2009; Isoo et al, 2016). Secondly, the ventilatory responses to acute hypoxia or hypercapnia become transiently blunted between P12 and P15 and exposure to chronic hypoxia during this period can prolong the hypoxic insensitivity; this suggests the TP may be an important step towards the development of some ventilatory functions (Liu et al, 2009; Teran et al, 2014; Bavis and MacFarlane, 2017).…”