Person:

Senft, Rebecca

Zebra finches (Taeniopygia guttata) learn to produce songs in a manner reminiscent of spoken language development in humans. One candidate gene implicated in influencing learning is the N-methyl-D-aspartate (NMDA) subtype 2B glutamate receptor (NR2B). Consistent with this idea, NR2B levels are high in the song learning nucleus LMAN (lateral magnocellular nucleus of the anterior nidopallium) during juvenile vocal learning, and decreases to low levels in adults after learning is complete and the song becomes more stereotyped. To test for the role of NR2B in generating song plasticity, we manipulated NR2B expression in LMAN of adult male zebra finches by increasing its protein levels to those found in juvenile birds, using a lentivirus containing the full-length coding sequence of the human NR2B subunit. We found that increased NR2B expression in adult LMAN induced increases in song sequence diversity and slower song tempo more similar to juvenile songs, but also increased syllable repetitions similar to stuttering. We did not observe these effects in control birds with overexpression of NR2B outside of LMAN or with the green fluorescent protein (GFP) in LMAN. Our results suggest that low NR2B subunit expression in adult LMAN is important in conserving features of stereotyped adult courtship song.

Changes in daylight amount (photoperiod) alter physiology and behaviour1,2. Adaptive responses to seasonal photoperiods are vital to all organisms – dysregulation associates with disease, from affective disorders3 to metabolic syndromes4. Circadian rhythm circuitry is implicated5,6 yet little is known about the precise cellular substrates underlying phase synchronization to photoperiod change. We present a previously unknown brain circuit and system of axon branch-specific and reversible neurotransmitter deployment that prove critical for behavioural and sleep adaptation to photoperiod. We found that the neuron type called mrEn1-Pet17 in the mouse brainstem Median Raphe Nucleus (MRN) segregates serotonin versus VGLUT3 (proxy for glutamate) to different axonal branches innervating specific brain regions involved in circadian rhythm and sleep/wake timing8,9. Whether measured during the day's light or dark phase, this branch-specific neurotransmitter deployment was indistinguishable; however, it reorganized on photoperiod change. Axonal boutons but not cell soma changed neurochemical phenotype upon shift away from equinox light/dark conditions that reversed upon return to equinox. When we genetically disabled Vglut3in mrEn1-Pet1 neurons, sleep/wake periods, voluntary activity, and clock gene expression failed to synchronize to the new photoperiod or were delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing, we delineated a Preoptic Area-to-mrEn1Pet1 connection responsible for decoding the photoperiodic inputs, driving the neurotransmitter reorganization and promoting behavioural synchronization. Our results reveal a previously unrecognized brain circuit and periodic, branch-specific neurotransmitter deployment that regulates organismal adaptation to photoperiod change.