Neural circuits of drive

We study how behavioural drives, like feeding, are regulated by hypothalamic and cortical neurons. The lateral hypothalamus is a key controller of feeding and other motivated behaviours. We recently discovered that it does not contain synaptically connected microcircuits, which are ubiquitous in the cortex. On the other hand, key parts of the cortex send input to the lateral hypothalamus. We study these neural pathways with slice electrophysiology and in vivo calcium imaging.

Control of motivated drives by the lateral hypothalamus

The lateral hypothalamus (LH) is a vital regulator of innate behavioral drives, homeostasis and brain arousal states [1] LH neurons promoting various, often competing behavioural actions, are intermingled with each other. They control behaviours through diffuse connections throughout the CNS. To understand how behavioural drives are organized into the adaptive patterns required to cope with the external milieu, we strive to address how activity of LH neurons is coordinated. We know that the spiking activity of LH neurons is modulated on a millisecond timescale, indicating that rapid synaptic input is important for this process [2].

However, we recently found that they do not communicate with each other through local synapses [3].

This relegates drive decisions to their long-range input circuits.

We are currently setting up our lab to study the long-range input to hypothalamus using quadruple whole-cell patch clamp recordings, optogenetic circuit dissection, in vivo 2-photon calcium imaging, freely-moving miniature microscope calcium imaging and anatomical tracing.

Selected Publications

[1] Burdakov, D., Karnani, M.M. & Gonzales, A. Lateral hypothalamus as a sensor-regulator in respiratory and metabolic control. Physiology & Behavior, 121, 117-24 (2013).

[2] Karnani, M.M., Schoene, C., Bracey, E., Viskaitis, P., Gonzalez, J.A., Adamantidis, A. & Burdakov, D. Role of Spontaneous and Sensory Orexin Network Dynamics in Rapid Locomotion Initiation. Progress in Neurobiology, 187, 101771 (2020).

[3] Burdakov, D. & Karnani, M.M. Ultra-sparse synaptic connectivity in the lateral hypothalamus. Current Biology doi: 10.1016/j.cub.2020.07.061 (2020).

[4] Jackson, J., Karnani, M.M., Zemelman, B.V., Burdakov, D. & Lee, A.K. Inhibitory control of Prefrontal Cortex by the Claustrum. Neuron 99, 1029-1039 (2018).

Team Leader
Mahesh Karnani