Biology subjects

Burdakov, D.

Publications and source records attributed to Burdakov, D..

22 records · Page 2Linked to original sources

bioRxiv2020

Ultra-sparse connectivity within the lateral hypothalamus

The lateral hypothalamus (LH) contains neuronal populations which generate fundamental behavioural actions such as feeding, sleep, movement, attack and evasion. Their activity is also correlated with various appetitive and consummatory behaviours as well as reward seeking. It is unknown how neural activity within and among these populations is coordinated. One hypothesis postulates that they communicate using inhibitory and excitatory synapses, forming local microcircuits. We inspected this hypothesis using quadruple whole cell recordings and optogenetics to screen thousands of potential connections in brain slices. In contrast to the neocortex, we found near zero connectivity within the LH. In line with its ultra-sparse intrinsic connectivity, we found that the LH does not generate local beta and gamma oscillations. This suggests that LH neurons integrate incoming input within individual neurons rather than through local network interactions, and that input from other brain structures is decisive for selecting active populations in LH.

neuroscience↗

bioRxiv2019

Rapid sensory integration in orexin neurons governs probability of future movements

Internally and externally triggered movement is crucial for survival and is controlled by multiple interconnected neuronal populations spanning many brain areas. Lateral hypothalamic orexin/hypocretin neurons are thought to play a slow, modulatory part in this scheme through their key role in promoting metabolism and wakefulness. However, it is unknown whether orexin/hypocretin neurons participate in rapid neural processing, leading to immediate movement. Furthermore, their role in sensorimotor transformations remains unknown. Here we use cellular-resolution Ca2+ imaging and optogenetics to show that orexin/hypocretin cells are instantaneous regulators of self-generated and sensory-evoked movement. They are activated before and during movement, preventing this activation reduces self-generated locomotion, and optogenetic mimicry of this transient activation rapidly initiates locomotion. We find that the same orexin neurons whose activity predicts movement initiation are rapidly controllable by external sensory stimuli, and silencing orexin cells during sensation prevents normal motor performance. These findings place orexin neurons in a physiological position of unexpectedly rapid and strong sensorimotor control.

neuroscience↗

bioRxiv2019

Natural hypothalamic circuit dynamics underlying object memorization

Memorizing encountered objects is fundamental for normal life, but the underlying natural brain activity remains poorly understood. The hypothalamus is historically implicated in memory disorders, but whether and how its endogenous real-time activity affects object memorization remains unknown. We found that upon self-initiated object encounters, hypothalamic melanin-concentrating hormone (MCH) neurons emit dynamic, object-encounter-associated signals encoding object novelty. Optosilencing of these signals, performed in closed-loop with object encounters selectively during object memory acquisition, prevented the ability to recognize the previously encountered objects. Optogenetic and chemogenetic connectivity analyses demonstrated that local GAD65 neurons form an inhibitory GAD65[->]MCH microcircuit that controls the object-encounter-associated MCH cell signals. GAD65 cell optosilencing during object memory acquisition enhanced future object recognition through MCH-receptor-dependent pathways. These results provide causal evidence that natural, object-associated signals in genetically-distinct but interacting hypothalamic neurons differentially control whether the brain forms object memories.

neuroscience↗

bioRxiv2018

The Homeostatic Logic of Reward

Energy homeostasis depends on behavior to predictively regulate metabolic states within narrow bounds. Here we review three theories of homeostatic control and ask how they provide insight into the circuitry underlying energy homeostasis. We offer two contributions. First, we detail how control theory and reinforcement learning are applied to homeostatic control. We show how these schemes rest on implausible assumptions; either via circular definitions, unprincipled drive functions, or by ignoring environmental volatility. We argue active inference can elude these shortcomings while retaining important features of each model. Second, we review the neural basis of energetic control. We focus on a subset of arcuate subpopulations that project directly to, and are thus in a privileged position to opponently modulate, dopaminergic cells as a function of energetic predictions over a spectrum of time horizons. We discuss how this can be interpreted under these theories, and how this can resolve paradoxes that have arisen. We propose this circuit constitutes a homeostatic-reward interface that underwrites the conjoint optimisation of physiological and behavioural homeostasis.

neuroscience↗