UNVEILING THE MECHANISMS OF LATERAL INHIBITION SUPPORTED BY ELECTRICAL SYNAPSES BETWEEN PRIMARY AFFERENTS

Electrical synaptic transmission relies on the direct flow of current between neurons, representing a widespread form of intercellular communication that is typically fast, bidirectional, and continuous. Beyond supporting synchronization and lateral excitation, electrical synapses can also mediate biphasic postsynaptic coupling potentials driven by spike afterhyperpolarizations (AHPs), consisting of a brief depolarizing phase followed by a longer-lasting hyperpolarization. In several neural structures, this biphasic response can result in net inhibitory postsynaptic effects. However, the mechanisms underlying this phenomenon and the contribution of active membrane properties of electrically coupled neurons remain poorly understood. Using the mouse Mesencephalic Trigeminal Nucleus, a structure composed of somatically-coupled proprioceptive primary afferent neurons, we show that activity in a single afferent neuron can strongly suppress spiking in an electrically coupled neighbor, thus supporting lateral inhibition. A single presynaptic action potential induces an inhibitory effect ranging from 1.5 to 20 ms, shaped by the combined contributions of both the depolarizing and hyperpolarizing phases of the coupling potential. Unexpectedly, the D-type potassium current (I_D) in both presynaptic and postsynaptic neurons plays a critical and dynamic role in this phenomenon. Presynaptically, I_D determines spike characteristics, particularly the AHP, thereby shaping the hyperpolarizing component of the spikelet. Postsynaptically, I_D is rapidly activated by the depolarizing phase, which in turn reduces neuronal excitability. Overall, our findings strongly suggest that electrical synapses can support lateral inhibition and reveal that primary afferent neurons actively participate in sensory processing, rather than serving solely as transmission lines.