Final Report Summary - CHEMOSENSORYCIRCUITS (Function of Chemosensory Circuits)
In this ERC project, we studied the function of chemosensory computations by focusing on 2 brain regions with very different properties, namely the habenula and the brainstem. The habenula is a brain region that is thought to be important for prediction of negative outcomes with a strong link with mood disorders such as anxiety and depression. The brainstem controls vital bodily functions such as feeding behavior, salivation, respiration, etc. It was previously unclear how chemosensory information is encoded in these regions and control animal behavior.
In work package 1, we discovered that odors are encoded in the habenula (Hb) in an asymmetric fashion, where odors activate neurons in the right Hb. We also showed that the odors with different valances elicit relatively similar activity in the dorsal Hb. Interestingly, we observed that the Hb exhibits a highly structured spontaneous activity, which is prominent even in the absence of sensory stimuli. Moreover, we also showed that chemosensory evoked activity as well as spontaneously generated activity in habenula represents functional clusters of Hb neurons that are born at distinct stages of development. This suggests that as animals develop more complex behaviors, the Hb circuitry gains new functions.
In parallel, we investigated the functional inputs to Hb, and showed that the olfactory bulb and zebrafish homologues of hippocampus (Dl) and amygdala (Dm) are the major brain regions that can drive habenula activity. We also found that the chemosensory inputs from the olfactory bulb and limbic inputs from the zebrafish homologues of the hippocampus and amygdala can strongly modulate each other. Moreover, we showed that learning can alter functional connectivity and the sensory representations in Hb and genetic ablation of Hb interferes with animals’ ability to remember their mistakes and learn new tasks.
In work package 2, we investigated how chemosensory/taste information is represented in the brainstem. We observed that different taste categories are encoded by the activation of very different clusters of neurons in the brainstem. Moreover, we observed that chemosensory information from different taste categories interacts with each other, where bitter taste suppresses the neural and behavioral response to other tastes, which is a mechanism likely to have evolved to protect animals from ingesting bitter (and therefore toxic) food.
In parallel, we investigated how chemosensory information in the brainstem is influenced by other sensory stimuli. To our surprise we did not find any multi-sensory interactions in the brainstem that can alter chemosensory representation. Hence, we took an alternative strategy and investigated the chemosensory representations in the zebrafish forebrain, where the zebrafish homologue of the gustatory cortex resides. We observed that aversive sensory stimuli, such as fearful odors, vibrations and heat are encoded by the activation of zebrafish homologue of amygdala; we are currently testing how such prior experience with aversive cues can alter the sensory representations in the zebrafish forebrain.
In brief, this ERC project allowed me to hire a multi-disciplinary team of engineers and life scientists, who developed novel technologies to monitor brain activity and animal behavior in juvenile zebrafish. My team introduced juvenile zebrafish with a richer behavioral repertoire as a rather unconventional model for neuroscience research, which is now getting more popular among the community. All these technical, and conceptional, advancements allowed me to establish my team at a world class institution, composed of successful life scientists, which are publishing high quality papers and now continue their scientific careers in top level institutions and industry, which is a good evidence for the knowledge transfer achieved by this ERC project.
In work package 1, we discovered that odors are encoded in the habenula (Hb) in an asymmetric fashion, where odors activate neurons in the right Hb. We also showed that the odors with different valances elicit relatively similar activity in the dorsal Hb. Interestingly, we observed that the Hb exhibits a highly structured spontaneous activity, which is prominent even in the absence of sensory stimuli. Moreover, we also showed that chemosensory evoked activity as well as spontaneously generated activity in habenula represents functional clusters of Hb neurons that are born at distinct stages of development. This suggests that as animals develop more complex behaviors, the Hb circuitry gains new functions.
In parallel, we investigated the functional inputs to Hb, and showed that the olfactory bulb and zebrafish homologues of hippocampus (Dl) and amygdala (Dm) are the major brain regions that can drive habenula activity. We also found that the chemosensory inputs from the olfactory bulb and limbic inputs from the zebrafish homologues of the hippocampus and amygdala can strongly modulate each other. Moreover, we showed that learning can alter functional connectivity and the sensory representations in Hb and genetic ablation of Hb interferes with animals’ ability to remember their mistakes and learn new tasks.
In work package 2, we investigated how chemosensory/taste information is represented in the brainstem. We observed that different taste categories are encoded by the activation of very different clusters of neurons in the brainstem. Moreover, we observed that chemosensory information from different taste categories interacts with each other, where bitter taste suppresses the neural and behavioral response to other tastes, which is a mechanism likely to have evolved to protect animals from ingesting bitter (and therefore toxic) food.
In parallel, we investigated how chemosensory information in the brainstem is influenced by other sensory stimuli. To our surprise we did not find any multi-sensory interactions in the brainstem that can alter chemosensory representation. Hence, we took an alternative strategy and investigated the chemosensory representations in the zebrafish forebrain, where the zebrafish homologue of the gustatory cortex resides. We observed that aversive sensory stimuli, such as fearful odors, vibrations and heat are encoded by the activation of zebrafish homologue of amygdala; we are currently testing how such prior experience with aversive cues can alter the sensory representations in the zebrafish forebrain.
In brief, this ERC project allowed me to hire a multi-disciplinary team of engineers and life scientists, who developed novel technologies to monitor brain activity and animal behavior in juvenile zebrafish. My team introduced juvenile zebrafish with a richer behavioral repertoire as a rather unconventional model for neuroscience research, which is now getting more popular among the community. All these technical, and conceptional, advancements allowed me to establish my team at a world class institution, composed of successful life scientists, which are publishing high quality papers and now continue their scientific careers in top level institutions and industry, which is a good evidence for the knowledge transfer achieved by this ERC project.