Abstract
In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. Acetylcholine is proposed as the salient signal that determines which memories are encoded but its actions on mossy fiber transmission are largely unknown. Here, we show experimentally that cholinergic receptor activation suppresses feedforward inhibition and enhances excitatory-inhibitory ratio. In reconstructions of CA3 pyramidal cells, this disinhibition enables postsynaptic dendritic depolarization required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how a combination of disinhibited mossy fiber activity, enhanced cellular excitability and reduced recurrent synapse strength can drive rapid overlapping ensemble formation. Thus, we propose a coordinated set of mechanisms by which acetylcholine release enables the selective encoding of salient high-density episodic memories in the hippocampus.
