Synapse- and cell-specific plasticity in the mature hippocampus
Queenan, Bridget Noelle
The central nervous system (CNS) is a living, breathing electrical circuit which learns and remembers by altering its own connectivity. Neurons, the electrical cells of the CNS, are thought to encode information by adjusting the strength of synaptic connections in an activity-dependent manner. Through processes known as associative synaptic plasticity (ASP), relevant synapses are strengthened, while irrelevant synapses are weakened, and the network learns the relationship between events. However, neural networks are stabilized by the seemingly contradictory force of homeostatic synaptic plasticity (HSP) and it is unclear how HSP can proceed without destroying information encoded at synapses by associative mechanisms. We studied the coexistence of HSP and ASP in the hippocampus, a highly plastic area of the mammalian brain essential for certain types of learning and memory.We observed both in vitro and in vivo that, in mature hippocampal networks, HSP occurred at a distinct subset of synapses, namely those between the mossy fibers (MF) of dentate granule cells and the thorny excrescences (TE) of proximal CA3 pyramidal neurons. MF-TE synapses are some of the largest, strongest, and most elaborate synapses in the CNS. MF terminals are selectively enriched in the presynaptic vesicle-associated protein, synaptoporin, and in endogenous opioids. We found that synaptoporin was necessary and sufficient for homeostatic adaptation of MF-TE synapses. We also observed that opioids bidirectionally and selectively regulated MF-TE homeostasis. Kappa opioid receptor (OR) signaling was necessary and sufficient for the upregulation of MF-TE in response to inactivity, while mu and delta OR signaling negatively constrained MF-TE synapses. Blockade of kappa OR signaling blocked homeostatic upregulation in vitro and delayed seizure progression in an animal model of temporal lobe epilepsy. Conversely, activation of kappa OR signaling mimicked homeostatic upregulation and exacerbated seizure progression.We concluded that MF-TE synapses act as hippocampal "volume control". The efficacy of MF-TE transmission can be homeostatically altered through designated signaling pathways, dynamically controlling the bandwidth of information entering downstream hippocampal networks which are free to encode information in distal dendrites via associative mechanisms. We therefore provide a new theory as to the coexistence of associative and homeostatic plasticity in the hippocampus.
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