Remodeling of reciprocal synapses associated with persistence of long‐term memory

Abstract

We investigated a model of long-term memory in which the female mouse establishes pheromonal memory of its partner at mating. We examined the reciprocal synapses of the accessory olfactory bulb and found that pheromonal memory was associated with morphological changes in excitatory synapses in the early phase of memory acquisition and by changes in inhibitory synapses in the late phases of memory persistence. After extinction of pheromonal memory, these morphological changes were no longer present. These findings suggest that the persistence of pheromonal memory is associated with continuous and dynamic changes in the morphological plasticity of reciprocal synapses in the accessory olfactory bulb.

Muscarinic receptor type 1 (M1) stimulation, probably through KCNQ/Kv7 channel closure, increases spontaneous GABA release at the dendrodendritic synapse in the mouse accessory olfactory bulb

“…The AOB dendrodendritic synapse is implicated in the plasticity of pheromonal memory (Brennan and Keverne, 1989;Kaba et al, 1994;Matsuoka et al, 2004). Female mice learn to give up responding to a mated male's pheromone at a critical period just after the mating and thereafter become insensitive to the pheromone (Leinders-Zufall et al, 2004).…”

“…Although AOB is not present in humans (Meisami et al, 1998), it is an attractive region for study because of its simple structure, consisting of only three types of neurones (Mori, 1987) and its implicated functions such as information integration (Xu et al, 2005;Hendrickson et al, 2008) or memory storage (Kaba et al, 1994;Matsuoka et al, 2004;Binns and Brennan, 2005).…”

α2-Adrenergic receptor activation promotes long-term potentiation at excitatory synapses in the mouse accessory olfactory bulb

“…A blockade of α-adrenergic receptors (ARs), but not β-ARs, in the AOB immediately after mating prevented the formation of the mate recognition memory (Kaba and Keverne 1988), as did the destruction of the noradrenergic innervation of the AOB prior to mating (Rosser and Keverne 1985). In addition, memory formation is associated with neurochemical and morphological changes at the MC-GC reciprocal synapses (Brennan et al 1995;Matsuoka et al 1997Matsuoka et al , 2004.…”

“…Prior electron-microscopic analyses revealed an increase in the length of the postsynaptic densities of the MC-to-GC glutamatergic side of the reciprocal synapses in the AOB, 24 h after the association of mating and exposure to male chemosignals (Matsuoka et al 1997(Matsuoka et al , 2004. Because such morphological changes may represent a morphological correlate of synaptic plasticity, we focused on the MC-to-GC excitatory synapse as a primary site for the modifiability of synaptic strength via LTP and other processes.…”

“…In addition to the enhancement of eEPSCs in GCs, the precisely timed action potentials generated in GCs would back-propagate into the dendrites, which presumably would provide the additional depolarization required to facilitate calcium influx through NMDA receptors and possibly voltage-gated calcium channels, leading to NMDA receptor-dependent LTP at the MC-to-GC side of the reciprocal synapses that are activated by the mate's chemosignals. The LTP would lead to a sequence of changes in the morphology of the reciprocal synapses (Matsuoka et al 1997(Matsuoka et al , 2004 and an increased release of the inhibitory neurotransmitter GABA in the AOB (Brennan et al 1995).…”