The zebrafish amygdala and hippocampus

Koichi Kawakami
The amygdala and hippocampus are two major components of the mammalian brains and perform crucial roles in the processing of emotional memory and episodic and spatial memory, respectively. In teleost, the medial and lateral zone of the dorsal telencephalon (Dm and Dl) have been postulated to be homologs of the mammalian amygdala and hippocampus based on neuroanatomical and functional studies. However, Dm and Dl are broad areas in the dorsal telencephalon and ! the neural circuitry mediating the amygdalar and hippocampal functions has yet to be explored. Here we identify the neuronal circuitry that is essential for emotional learning and episodic and spatial learning by a genetic approach in zebrafish. We performed large-scale gene trap and enhancer trap screens and generated transgenic fish that expressed Gal4FF, a synthetic Gal4 transcription activator, in specific regions and neuronal circuits in the brain. Then we crossed these brain-specific Gal4FF transgenic fish lines with UAS-neurotoxin lines to inhibit the activity of the Gal4FF-expressing neurons, and analyzed behaviors of the double transgenic fish. We found that, when the activity of a subpopulation of neurons in the Dm or Dl was inhibited, the fish showed deficits in emotional learning (fear conditioning) or episodic (trace fear conditio! ning) and spatial learning paradigms. Thus, we think that thes! e neuronal populations are functional equivalents of the mammalian amygdala and hippocampus, respectively. This finding provides a basis for understanding essential neuronal circuits mediating evolutionarily conserved behaviors in vertebrates and investigating neurological diseases associated with amygdala and hippocampus pathology, such as anxiety disorders, epilepsy and Alzheimer’s disease by using the model vertebrate zebrafish.