Regulation of Synaptic Strength & Circuit Dynamics
For conceptual purposes, it has been convenient and popular to subdivide synaptic plasticity into two categories: Hebbian plasticity that is synapse-specific and induced within minutes, and homeostatic synaptic scaling that is neuron-wide, specific to the postsynaptic neuron, and induced by changes in activity over several hours or longer. Homeostatic scaling is thought to act like an overall gain control to keep neurons away from non-informative extremes of maximal firing or silence.
In the Tsien Lab, we think the rationale is good (see Liu and Tsien, 1995) and that there is some truth to the specific scenario, but have made experimental observations that lead us to a different worldview. We believe that in a network adapting to chronic inactivity (1) some of the biggest changes are presynaptic, not just postsynaptic; (2) induction of the changes can be initiated postsynaptically; (3) the changes are not uniformly implemented across all synapses given or received by a neuron; and (4) the guiding principle is a kind of zero sum game, wherein some boutons on an axon (or spines on a dendritic branch) get stronger while others are weakened or silenced.
Whether this is conceptualized as competition for or sharing of signaling resources such as vesicles or release machinery, it is critical to decipher its computational impact. Supporting important connections while weakening others nearby may give neurons and networks their best opportunity to balance information processing and stability. Working out the key cell biological mechanisms underlying plasticity and synaptic scaling is a major challenge for the future.
Kim J and Tsien RW. Synapse-specific adaptations to inactivity in hippocampal circuits acheive homeostatic gain control while dampening network reverberation. Neuron. 2008. DOI.
We characterized inactivity-induced adaptations at three sets of excitatory synapses in TTX-treated organotypic hippocampal cultures. Dentate-to-CA3 and CA3-to-CA1 synapses were upregulated, confirming homeostatic gain control. However, in disagreement with conventional homeostasis predictions, the recurrent CA3-to-CA3 synapses were downregulated. This change contributed to shortening of reverberatory bursts generated by feedforward excitation and protected against runaway excitation.
Mitra A … Tsien, RW. Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity. Nature Neuroscience. 2012. DOI.
Recurrent excitatory circuits face extreme challenges in balancing efficacy and stability. We recorded data from CA3 pyramidal neuron pairs in rat hippocampal slice cultures to characterize synaptic and circuit-level changes in recurrent synapses resulting from long-term inactivity. Our results suggest that recurrent circuits adapt to chronic inactivity by reallocating presynaptic weights heterogeneously: some connections are strengthened while others are silenced. The silencing is shown to result from enhanced Cdk5 activity.