| Description |
A challenge to correlating structure with function in the vertebrate brain is the lack of detailed information about diverse neuronal subtypes and the connections that they make. My laboratory has taken two complementary approaches to develop tools for neuronal identification and manipulation in the zebrafish brain. First, we have adapted the Q transcriptional regulatory system of Neurospora crassa for zebrafish transgenesis and are testing a binary gene/enhancer trap strategy designed to label neurons selectively. This will also allow neuronal populations to be activated, silenced or Ablated without affecting other tissues.
The second approach has been to focus on a conserved forebrain-midbrain pathway, the habenulointerpeduncular (Hb-IPN) conduction system, and perform RNA-seq analyses to obtain new markers of neuronal cell types. This has led to the discovery of a somatostatinergic population in the dorsal habenulae that innervates a ventrally restricted sub region of the interpeduncular nucleus (IPN). Transcriptional profiling of the IPN has revealed regional differences in gene expression that will allow the identity and connectivity of its distinct sub regions to be resolved. Ultimately, the goal is understand the functions of neuronal subsets in the Hb-IPN system. Using genetically encoded calcium indicators, we have been imaging the larval habenulae following exposure to an aversive stimulus as a means of correlating patterns of activation with defined neuronal subtypes. The zebra fish thus provides a unique model for determining the activity as well as the identity of neuronal populations underlying defined behavioral responses.
|