| Popis: |
Habituation allows animals to learn to ignore persistent but inconsequential stimuli. Despite being the most basic form of learning, a consensus model on the underlying mechanisms has yet to emerge. To probe relevant mechanisms we took advantage of a visual habituation paradigm in larval zebrafish, where larvae reduce their reactions to abrupt global dimming (a dark flash). Using Ca2+ imaging during repeated dark flashes, we identified 12 functional classes of neurons that differ based on their rate of adaptation, stimulus response shape, and anatomical location. While most classes of neurons depressed their responses to repeated stimuli, we identified populations that did not adapt, or that potentiated their response. To identify molecular players, we used a small molecule-screening approach to search for compounds that alter habituation learning. Among the pathways we identified were Melatonin and Estrogen signaling, as well as GABAergic inhibition. By analyzing which functional classes of neurons are GABAergic, and the result of pharmacological manipulations of the circuit, we propose that GABAergic inhibitory motifs drive habituation, perhaps through the potentiation of GABAergic synapses. Our results have identified multiple molecular pathways and cell types underlying a form of long-term plasticity in a vertebrate brain, and allow us to propose the first iteration of a model for how and where this learning process occurs. |
