Current Projects

Cortical oscillations in animal models of schizophrenia

Contemporary views of schizophrenia regard cognitive dysfunction as the primary core deficit due to dysfunction of neuronal microcircuits. Brain oscillations are known to be critical for cognitive processes and their alterations in schizophrenic patients were proposed to significantly contribute to the neurocognitive impairments characteristic for this disease. This project examines the functioning of neuronal networks involved in cortical oscillations in neurodevelopmental animal models of schizophrenia in an attempt of finding a link between the structural changes and neurocognitive deficits. Our recent focus is on the impaired rhythmic coordination between activities in the hippocampus (HC) and prefrontal cortex (PFC) which is particularly important for specific cognitive functions in the adult and was also shown to play an important role in early neurodevelopment. Abnormal functional connectivity between HC and PFC has been demonstrated in schizophrenic patients and in chronic animal models of schizophrenia. Since pathological alterations of the key elements of neuronal oscillatory networks are present in both HC and PFC, impaired cortico-hippocampal synchronization can originate from the pathology of either or both structures. We propose to examine this issue using a novel approach that can precisely define the spatial distribution of rhythmic generators and quantify their interactions, including the essential directional influences. This work will increase our neuronal level understanding of the mechanisms of cognitive deficits in schizophrenia which will facilitate the development of new strategies for drug development.

Subcortical regulation of hippocampal oscillations, the effect of psychoactive drugs

The central focus of this project is the subcortical regulation of hippocampal function and is guided by the general hypothesis that the role of this regulation is to build dynamic associations between several limbic structures synchronized by oscillatory population activity. The general state and background activity of various brain structures determine how these structures will respond to different specific inputs and how they establish dynamic connections to perform complex functions. An important constituent of these states is the pattern of population activity including coherent oscillations in anatomically scattered structures which can establish functional networks during specific behaviors. Theta synchrony provides an excellent model to study these cooperations and the way in which they differ in specific behavioral states, such as waking exploration and REM sleep. The characteristic involvement of various neuromodulators also facilitates using this model to investigate the effect of psychoactive drugs on the level of neuronal ensembles and networks.


Cognitive deficits in anorexia nervosa: evaluation of neuronal mechanisms in a rodent model

Anorexia nervosa (AN) is a life-threatening eating disorder that encompasses a broad range of psychological symptoms. It is also associated with significant cognitive impairments and psychiatric comorbidity. This project will study the neuronal circuits and neurotransmitters that have been associated with cognitive deficits in anorexia patients with the ultimate goal of better understanding of the pathology of the disease and to help finding novel therapeutic options. In this study we use the rodent activity-based anorexia (ABA) model which mimics the core features of AN. A major advantage ABA has over other models is its behavioral nature, i.e. rats “voluntarily choose” to conduct the deleterious anorexic-like behavior, suggesting that the model’s validity may extend beyond the hypothalamic feeding circuits and can thus provide useful information about the forebrain mechanisms of executive control which in AN override the hypothalamic homeostatic regulation. From recent neuropsychological investigation of AN patients, applying a large battery of standardized tests, attentional set-shifting (ASST) deficits appear to emerge as a quantifiable measure of clinically observed cognitive inflexibility which may manifest as stereotyped or rigid behavior of controlling weight. Human ASST tasks have standard, well-established rodent analogues which allow investigation of the neuronal mechanisms of this deficit in animal models of AN. We are evaluating ASST performance and, as ASST critically depends on prefrontal cortex (PFC), investigate PFC activity after the development of ABA and then, after recovery, in female rats.