Neurons propagate information through circuits by integrating thousands of synaptic inputs to generate an action potential output. Inputs from different origins are often targeted to distinct regions of a neuron's dendritic tree, with synapses on more distal dendrites normally having a weaker influence on cellular output compared to synapses on more proximal dendrites. Here, we report that hippocampal CA2 pyramidal neurons, whose function has remained obscure for 75 years, have a reversed synaptic strength rule. Thus, CA2 neurons are strongly excited by their distal dendritic inputs from entorhinal cortex but only weakly activated by their more proximal dendritic inputs from hippocampal CA3 neurons. CA2 neurons in turn make strong excitatory synaptic contacts with CA1 neurons. In this manner, CA2 neurons form the nexus of a highly plastic disynaptic circuit linking the cortical input to the hippocampus to its CA1 neuronal output. This circuit is likely to mediate key aspects of hippocampal-dependent spatial memory.
► CA2 neurons mediate a disynaptic link between cortex and hippocampal CA1 neurons ► CA2 neurons receive strong convergent excitation from LII and LIII entorhinal neurons ► CA2 neurons make strong excitatory synapses with CA1 neurons ► Entorhinal inputs onto CA2 show strong LTP
