In the cerebral cortex, diverse types of neurons form intricate circuits. Combinatorial interactions between two neurons could maximize synaptic diversity and may be relevant for the processing and storage of information. Relative to excitatory glutamatergic neurons, inhibitory GABAergic neurons are highly diverse. How such heterogeneity of GABAergic neurons defines functional specificity of GABAergic synapses is largely unknown. Using multiple recordings in rodent brain slices, we identified two distinct organizing principles for GABAergic synapses in the amygdala and hippocampus.
Based on the electrophysiological evidence from multiple neuron recordings, we found that the type of synapse used by each neuron in an amygdala inhibitory microcircuit to influence its neighbors follows three functional organizing principles. First, each class of neurons forms specific synapses onto a given target neuron (synapse mapping principle). Second, the phenotypic nature of both presynaptic and postsynaptic neurons is involved in determining the type of synapse formed (interaction principle). Third, presynaptic neurons form synapses with similar properties onto neighboring target neurons of the same type (synapse homogeneity principle). Intriguingly, these organizing principles are circuit-specific. Unlike differential signaling via the same axon of inhibitory neurons (synapse mapping principle), interneurons in the hippocampus display presynaptic homogeneity. Each class of inhibitory interneurons in the dentate gyrus forms synapses with almost stereotyped temporal dynamics onto different types of target neurons. Furthermore, unlike the interaction principle found in the amygdala, presynaptic cell types alone govern specificity of temporal dynamics of synapses. Together, distinct organizing principles of GABAergic synapses in the amygdala and hippocampus reveal different network mechanisms in regulating memory microcircuits.