UC San Diego

Glutamatergic excitatory synapses are one of the main currencies of the mammalian central nervous system. Excitatory synapses have been most well-characterized in terms of dendritic spines, which are small membranous protrusions. Dendritic spines influence synapse function by boosting synaptic potentials and sequestering synaptically-generated second messengers. Spines have been extensively studied in densely spiny principal neurons, but little is known about how they expand the information-gathering capabilities of sparsely spiny interneurons (INs). We find in the mouse primary visual cortex, parvalbumin-positive INs have a low density of spines that enclose functional glutamatergic synapses. Both spine and dendritic synapses contain calcium-permeable AMPA and NMDA receptors (CP-AMPARs, NMDARs), but NMDARs are enriched at spine synapses. Despite these similarities, spine synapses are embued with distinct sensitivities to the ongoing activity of the neuron. Glutamate receptor-mediated calcium (Ca) influx at proximal dendritic sites is bi-directionally modulated by the timing of action potentials (APs). Surprisingly, spine synapses are largely insensitive to APs but coincident activity originating in the adjacent dendrite strongly influences spine NMDAR-mediated Ca influx. Thus, while glutamate receptors on spines and dendrites are modulated by the activity of the neuron, they are distinctive in the type of coincident activity detected.