Susceptibility for homeostatic plasticity is down‐regulated in parallel with maturation of the rat hippocampal synaptic circuitry

Abstract

Homeostatic regulation, i.e. the ability of neurons and neuronal networks to adjust their output in response to chronic alterations in electrical activity is a prerequisite for the pronounced functional plasticity in the developing brain. Cellular mechanisms of homeostatic plasticity have mainly been studied in cultured preparations. To understand the developmental time frame and properties of homeostatic plasticity under more physiological conditions, we have here compared the effects of activity deprivation on synaptic transmission in acutely isolated and cultured hippocampal slices at different stages of development. We find that transmission at both glutamatergic and GABAergic synapses is strongly and rapidly (15 h) regulated in the opposite directions in response to inactivity during narrow, separated time windows early in development. Following this critical period of synaptic development, induction of the homeostatic response requires longer periods (40 h) of inactivity. At glutamatergic synapses, activity blockade led to an increase in the amplitude and frequency of mEPSCs, and the threshold for induction of this response was increased during development. In contrast, homeostatic regulation at GABAergic synapses was expressed in a qualitatively distinct manner at different developmental stages. Immature neurons responded rapidly to inactivity by regulating mIPSC frequency, while longer activity blockade led to a decrease in the mIPSC amplitude independent of the neuronal maturation. The susceptibility of immature networks to homeostatic regulation may serve as a safety mechanism against rapid runaway destability during the time of intense remodelling of the synaptic circuitry.

Activity-Dependent Ubiquitination of GABAAReceptors Regulates Their Accumulation at Synaptic Sites

“…In contrast, blockade of synaptic activity in developing hippocampal neurons does not appear to modify the number of cell surface GABA A Rs or their accumulation at synaptic sites (Harms and Craig, 2005). This discrepancy may reflect the varying ages of the culture preparations used (Huupponen et al, 2007) or the length of activity blockade, 24 h compared with 18 d. Intriguingly, it has been demonstrated recently that exposure of cultured neurons to TTX over a period of 7-14 d results in retraction of dendrites and a loss of spines (Fishbein and Segal, 2007). Therefore, this phenomenon may complicate the analysis of the long-term effects of activity blockade on the formation of inhibitory synapses.…”

Homeostatic plasticity mechanisms are required for juvenile, but not adult, ocular dominance plasticity

“…For example, in the rat hippocampus, a period of in vivo activity blockade by TTX application results in scaling-up of pyramidal neuron mEPSC amplitudes in juvenile animals, but has no effect on mEPSC amplitude in adults (18), whereas the susceptibility to TTX incubation-induced scaling-up of mEPSC amplitude declines significantly between P4 and P8 (17). Interestingly, a nonmultiplicative form of DE-induced synaptic plasticity, which comprises a nonuniform increase in synaptic weights, has been reported to persist into adulthood in L2/3 of the mouse visual cortex (16).…”

“…One study has suggested that a form of synaptic scaling persists into adulthood in layer 2/3 (L2/3) of the visual cortex (16). On the other hand, studies in the hippocampus have shown that homeostatic plasticity, and synaptic scaling in particular, are down-regulated during development (17,18).…”

High Firing Rate of Neonatal Hippocampal Interneurons Is Caused by Attenuation of Afterhyperpolarizing Potassium Currents by Tonically Active Kainate Receptors

“…Since interneurons are the key players in setting the temporal coherence critical for synaptic plasticity and neuronal network oscillations, a mechanism that could switch the interneuronal firing pattern from "newborn" to "adult" type would have a privileged role in the activitydependent maturation of the brain. There are several reports demonstrating the critical role of early hippocampal network bursts in guiding synaptic maturation (Lauri et al, 2003;Huupponen et al, 2007) and the instrumental role of interneurons in synchronizing this activity Palva et al, 2000, Ben-Ari et al 2004). Thus, our findings disclose a critical endogenous mechanism controlling the level of interneuronal output during development that can be of vital importance in the development of functional synaptic circuits in the hippocampus.…”