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Research

1
Stress Circuitry and Regulation

The biological response to stress is concerned with the maintenance of homeostasis in the presence of real or perceived challenges. This complex process requires numerous adaptive responses, involving changes in the central nervous system and neuroendocrine system. When a situation is perceived as stressful, the brain activates multiple neuronal circuits, linking areas involved in sensory, motor, autonomic, neuroendocrine, cognitive, and emotional functions in order to adapt to the demand. Currently the details of the pathways by which the brain translates stressful stimuli into an integrated biological response are only partially understood. We study specific genes and brain circuits which are associated with or altered by the stress response, to gain a better and broader understanding of the neurobiology of stress. These studies could provide important insights into the way stress affects physiological and psychological disorders.

2
Stress Linked Psychopathologies

Dysregulation of the behavioral and neuroendocrine responses to stressors can have severe psychological and physiological consequences. A wealth of evidence suggests that inappropriate regulation, disproportional intensity, or chronic and/or irreversible activation of the stress response is linked to the etiology and pathophysiology of anxiety disorders and depression. Current research in the lab focuses on studying the central pathways and molecular mechanisms mediating the stress response and the related psychopathologies. Defining the contribution of known and novel gene products to the maintenance of stress-linked homeostasis could improve our ability to design therapeutic interventions for stress-related psychiatric disorders.

3
Gene X stress Interaction: Epigenetic Mechanisms

Most psychiatric disorders display a strong genetic component, but heritability can only partially explain an individual’s risk to develop such a disorder. Only a few specific gene mutations have been directly linked to increased susceptibility for mental illness. Environmental factors — mainly exposure to psychological or physiological stressors — have been associated in epidemiological studies with psychiatric morbidity. For example, stress in-utero or during early life might program brain vulnerability to particular psychiatric disorders, while stress in adolescence or later in life might trigger the onset of such disorders. Thus, a complex interaction between genetic predisposition and environmental factors is suggested to be at the root of mental illness. Environmental factors can induce changes in gene expression levels that might mediate the onset of a disease without altering the DNA sequence, through epigenetic mechanisms. These mechanisms include histone modification, DNA methylation, and post-transcriptional regulation by RNA methylation and non-coding RNAs. Elucidating the role of epigenetic processes in mediating central nervous system functions could lead to a better understanding of the mechanisms of psychiatric disorders, and could thereby promote much-needed breakthroughs in the development of new drug targets and biomarkers for these illnesses.

4
Early Life Stress

Early life environmental factors affect developing systems, and may permanently alter organ structure and function throughout life. The central and peripheral organs that play pivotal roles in the body’s response to stress and the maintenance of homeostasis are key targets for such effects. Substantial evidence links early life stress to the etiology and pathophysiology of anxiety disorders, depression, and cognitive dysfunction later in life. Nevertheless, the pathways by which the brain is programmed to translate stressful stimuli into the final, integrated biological response are not fully understood. Current research in the lab focuses on the brain circuits and genes which are associated with or altered by prenatal and perinatal stress, aiming to better understand the mechanisms by which early life stress affects psychological and neuroendocrine disorders.

5
Complex Behavior

The behavior of an organism is determined by both its genetic makeup and influences from its environment. Neurobiological processes play a key role in translating genetic predispositions into complex behavioral traits, as well as in modulating behavior under a variety of conditions. However, these processes are still only partially understood, and bridging the gap between genotype and behavior is one of the foremost challenges in the field of neuroscience. Current research in the lab focuses on complex social behavior, observing and tracking multiple behavioral readouts in groups of normal or mutant mice, under various conditions, in an enriched environment. This approach allows us to obtain and analyze large amounts of naturalistic behavioral data, in high spatial and temporal resolution. Improving knowledge of the subtle ways in which genes and pathways influence behavior in a social context could lead to better understanding and treatment of disorders affecting social behavior, such as social anxiety disorder and autism.

6
Metabolism and stress

Maintaining energy homeostasis in the presence of real or perceived challenges is a complex task, reliant on multiple adaptations in the neuroendocrine and central nervous systems. Energy homeostasis is ultimately governed by the brain, where a variety of incoming signals about the organism’s nutritional state and its external environment are integrated to modulate pathways that control feeding behavior and energy expenditure. Ongoing research in the lab aims to determine the role of components of the stress system in these processes under normal and stressful conditions. Understanding the contributions of the CRF family of ligands and receptors to the maintenance of homeostasis and to stress-linked allostasis could improve our ability to design therapeutic interventions for metabolic disorders and related psychological disorders.

News

Semi-natural setups can contribute to a more complete understanding of dominance and aggression in mice.

Checkout our latest review in Current Opinion in Neurobiology.
 

Group social dynamics in a semi-natural setup reveal an adaptive value for aggression in male mice.

Environmental enrichment and oxytocin knockout show opposite effect on aggression and hierarchy structure in male mice.

Sex shapes cell-type-specific transcriptional signatures of stress exposure in the mouse hypothalamus

Our latest publication in Cell Reports shows that the response to acute stress is encoded differently in cell types and sexes.

Recent Publications

Shemesh Y, Benjamin A, Shoshani-Haye K, Yizhar O, Chen A.
Studying dominance and aggression requires ethologically relevant paradigms. Science Direct. doi: 10.1016/j.conb.2024.102879.

Anpilov S, Shemesh Y, Benjamin A, Biagini T, Sztainberg Y, Richter-Levina A, Forkosh O, Chen A.
Group social dynamics in a semi-natural setup reveal an adaptive value for aggression in male mice. bioRxiv. doi: 10.1101/2024.04.25.591070.

Scientist Spotlight

Dr. Maya Amitai

Consultant
Congratulations to Maya on completing her PhD! She is now a triple doctor holding an MD and two PhDs. Well done Maya!