FIRE TOGETHER: ELECTRICAL COUPLING SYNCHRONIZES SLOW OSCILLATIONS AND ACTION POTENTIALS IN THE RAT HYPOTHALAMIC TUBEROINFUNDIBULAR DOPAMINE (TIDA) NETWORK

Neuroendocrine tuberoinfundibular dopamine (TIDA) neurons control reproductive behaviour and physiology through tonic inhibition of the pituitary's prolactin release. The efficiency of this inhibition is reflected in the low basal prolactin levels in male rats, where TIDA neurons exhibit highly rhythmic, slow oscillations between periods of discharge (UP States) and relative hyperpolarization and quiescence (DOWN States), synchronized by electrical synapses within the network. However, a detailed analysis of TIDA circuit dynamics and whether gap junctions also synchronize the discharge of individual action potentials (APs) in the TIDA neurons remains unknown. We addressed this issue using dual whole-cell patch-clamp recordings of TIDA neurons in slices from male THcre-tdTomato rats (P21-30) and calcium imaging from slices of THcre rats (P56-70) injected with AAV-DIO-jGCaMP8m. Spike-time cross-correlation analysis revealed that AP synchronicity correlated with the strength of electrical coupling: r_P=0.92, p<0.0001, n=30 pairs. Calcium dynamics at the TIDA population level revealed a high level of network synchrony: 83±4 % of significantly correlated pairs with a cross-correlation coefficient (at lag 0 ms) of 0.53±0.01 n=8/3 slices/animals. Electrophysiological and dye coupling experiments showed that a single TIDA neuron could be coupled to more than one neuron and generate discrete amplitudes of spikelets, which were abolished by the blocker of voltage-gated Na⁺ channels, tetrodotoxin. Additionally, hyperpolarization-induced silencing of the prejunctional neuron eliminated spikelets in the postjunctional neuron. Thus, gap junctions regulate TIDA circuit synchronization on a faster time scale than previously assumed and might be critical for the efficient dopamine release and hormonal homeostasis.