Abstract
Homeostatic plasticity is thought to be important in preventing neuronal circuits from becoming hyper- or hypoactive. However, there is little information concerning homeostatic mechanisms following in vivo manipulations of activity levels. We investigated synaptic scaling and intrinsic plasticity in CA1 pyramidal cells following 2 days of activity-blockade in vivo in adult (postnatal day 30; P30) and juvenile (P15) rats. Chronic activity-blockade in vivo was achieved using the sustained release of the sodium channel blocker tetrodotoxin (TTX) from the plastic polymer Elvax 40W implanted directly above the hippocampus, followed by electrophysiological assessment in slices in vitro. Three sets of results were in general agreement with previous studies on homeostatic responses to in vitro manipulations of activity. First, Schaffer collateral stimulation-evoked field responses were enhanced after 2 days of in vivo TTX application. Second, miniature excitatory postsynaptic current (mEPSC) amplitudes were potentiated. However, the increase in mEPSC amplitudes occurred only in juveniles, and not in adults, indicating age-dependent effects. Third, intrinsic neuronal excitability increased. In contrast, three sets of results sharply differed from previous reports on homeostatic responses to in vitro manipulations of activity. First, miniature inhibitory postsynaptic current (mIPSC) amplitudes were invariably enhanced. Second, multiplicative scaling of mEPSC and mIPSC amplitudes was absent. Third, the frequencies of adult and juvenile mEPSCs and adult mIPSCs were increased, indicating presynaptic alterations. These results provide new insights into in vivo homeostatic plasticity mechanisms with relevance to memory storage, activity-dependent development and neurological diseases.
Highlights
Activity-dependent Hebbian plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), is thought to have an inherently positive feed-back component that tends to destabilize neuronal networks [1,2,3]
It has been shown that visual cortical neurons in culture respond to decreased levels of activity imposed by prolonged TTX application with scaling up of miniature excitatory postsynaptic current amplitudes and scaling down of miniature inhibitory postsynaptic currents [8,19,20]
Two days after Elvax implantation, extracellular field potentials were recorded from the CA1 pyramidal layer in acute slices, in response to electrical stimulation of the stratum radiatum at various stimulation intensities, and the population spike amplitude of the field excitatory post-synaptic potential was measured, representing the synchronized firing of cells
Summary
Activity-dependent Hebbian plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), is thought to have an inherently positive feed-back component that tends to destabilize neuronal networks [1,2,3]. Imposed decreases in activity in cultured hippocampal cells tend to lead to generally similar alterations as in cultures of the visual cortex, including neuronal hyperexcitability, increased glutamatergic transmission and decreased GABAergic synaptic inputs [4,7,16,19,21,22], indicating the generality of homeostatic responses. Such activity-dependent changes are interpreted to be homeostatic because the direction of the alterations are such that they appear to counteract the imposed change in activity, resulting in stabilization of firing rates within the appropriate ranges [2]
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