The critical period: neurochemical and synaptic mechanisms shared by the visual cortex and the brain stem respiratory system

Abstract

The landmark studies of Wiesel and Hubel in the 1960's initiated a surge of investigations into the critical period of visual cortical development, when abnormal visual experience can alter cortical structures and functions. Most studies focused on the visual cortex, with relatively little attention to subcortical structures. The goal of the present review is to elucidate neurochemical and synaptic mechanisms common to the critical periods of the visual cortex and the brain stem respiratory system in the normal rat. In both regions, the critical period is a time of (i) heightened inhibition; (ii) reduced expression of brain-derived neurotrophic factor (BDNF); and (iii) synaptic imbalance, with heightened inhibition and suppressed excitation. The last two mechanisms are contrary to the conventional premise. Synaptic imbalance renders developing neurons more vulnerable to external stressors. However, the critical period is necessary to enable each system to strengthen its circuitry, adapt to its environment, and transition from immaturity to maturity, when a state of relative synaptic balance is attained. Failure to achieve such a balance leads to neurological disorders.

Keywords: BDNF; GABAergic inhibition; critical period; postnatal development; synaptic imbalance.

Figure 1.

Mean amplitudes and frequencies of sIPSCs (a,b) and sEPSCs (c,d) were recorded daily (P14–P36) from layer V pyramidal neurons of the rat visual cortex. Circled regions denote the critical period when amplitudes and frequencies of sIPSCs rise sharply while those of sEPSCs fall steeply from P28 until P34, when all returned to P27 levels (modified from [22]). Mean sIPSCs (e,f) and sEPSCs (g,h) in respiratory neurons during postnatal development. Circled time points (P12–13) represent the critical period when sIPSCs rise significantly while sEPSCs fall drastically (modified from [36]). ***p < 0.001; **p < 0.01; *p < 0.05 (Tukey's test comparing adjacent age groups). (Online version in colour.)

Figure 2.

Optical densitometric analysis of BDNF immunoreactivity in single neurons of (a) layers II to VI of the rat visual cortex, daily, from P14 toP36 (modified from [22]) and (b) a respiratory nucleus in the rat brain stem from P0 to P21 (modified from [51]). Circled regions highlight the critical periods when the level of BDNF is significantly reduced. **p < 0.01; *p < 0.05 (Tukey's test). (Online version in colour.)

Figure 3.

Summary diagram of major developmental events before, during and after the critical period. The critical period is marked by synaptic imbalance, with enhanced inhibition and suppressed excitation, aided by reduced BDNF/TrkB expression. The imbalance can be reversed or accentuated by TrkB agonist or antagonist, respectively.