INTERNSHIP OFFER, Karnani lab, academic year 2020-21
MASTER PROJECT: Routing of top-down drive control connections
The lateral hypothalamic area (LHA) is a vital regulator of innate behavioral drives, homeostasis and brain arousal states . LHA neurons promoting various, often competing behavioral actions, are intermingled with each other [2–4]. To understand how behavioral drives are organized into the adaptive patterns required to cope with the external milieu, we need to address how activity of LHA neurons is coordinated. We know that the activity of LHA neurons is modulated on a millisecond timescale, indicating that synaptic input is key . However, we recently found that they do not communicate with each other through local synapses . This relegates drive decisions to their long-range input circuits.
Two key areas projecting to LHA are the medial prefrontal cortex (mPFC) and olfactory cortex (OlfC), which are expected to underly cognitive and innate control of behavioral drives. These also project to numerous other brain regions involved in shaping motivated behaviors. This project will study the routing of signals from mPFC and OlfC to LHA and other targets. You will use anatomical tracers such as CTB and adenoviral tracers  to find out whether dedicated mPFC and OlfC neurons communicate to LHA, and whether dedicated LHA neurons specialize in receiving input from only mPFC or OlfC. You will learn to do cryosectioning, brain clearing with CLARITY/PACT and confocal/light sheet imaging.
Students must have a strong interest in experimental neuroscience, have studied the papers listed here and be prepared to read much more. For applications we request: (i) a statement of motivation, (ii) a curriculum vitae, (iii) the names and emails of 2 academic references.
- Bonnavion P, Mickelsen LE, Fujita A, de Lecea L, Jackson AC. Hubs and spokes of the lateral hypothalamus: cell types, circuits and behaviour. The Journal of Physiology. 2016;594: 6443–6462. doi:10.1113/JP271946
- Li Y, Zeng J, Zhang J, Yue C, Zhong W, Liu Z, et al. Hypothalamic Circuits for Predation and Evasion. Neuron. 2018;97: 911–924.e5. doi:10.1016/j.neuron.2018.01.005
- Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature. 2007;450: 420–4. doi:10.1038/nature06310
- Konadhode RR, Pelluru D, Blanco-Centurion C, Zayachkivsky A, Liu M, Uhde T, et al. Optogenetic Stimulation of MCH Neurons Increases Sleep. Journal of Neuroscience. 2013;33: 10257–10263. doi:10.1523/JNEUROSCI.1225-13.2013
- Karnani MM, Schöne C, Bracey EF, González JA, Viskaitis P, Li H-T, et al. Role of spontaneous and sensory orexin network dynamics in rapid locomotion initiation. Prog Neurobiol. 2020;187: 101771. doi:10.1016/j.pneurobio.2020.101771
- Burdakov D, Karnani MM. Ultra-sparse connectivity within the lateral hypothalamus. bioRxiv. 2020; 2020.04.25.061564. doi:10.1101/2020.04.25.061564
- Saleeba C, Dempsey B, Le S, Goodchild A, McMullan S. A Student’s Guide to Neural Circuit Tracing. Front Neurosci. 2019;13. doi:10.3389/fnins.2019.00897