Throughout life animals inevitably encounter unforeseen threatening events. Activity of principal cells in the hippocampus is tuned for locations and for salient stimuli in the animals’ environment thus, forming a map known to be pivotal for guiding behavior. Here, we investigate if a code corresponding to threatening stimuli exists in the CA1 region of the dorsal hippocampus.
Active research and clinical experience have shown that the uncontrolled immune response to Sars-Cov-2 is characterized in many cases by a devastating cytokine storm (Chaolin Huang 2020). Morbidity and mortality are in part a consequence of this inflammatory response in the body (Ye Q 2020). The course of the disease is known to be more severe in pregnant women (Kathryn M Moore 2021), however, the effect of SARS-CoV-2 on the developing fetus is currently unclear. Case studies show that vertical transmission is rare, however, several studies support that placental and fetal infections may occur (Chen H 2020), (Dong L 2020), (Patanè L 2020). Several clinical manifestations of Covid-19 infection in the nervous system have also been reported recently (Desforges M. 2020), (Bohmwald K. 2018).
In vivo two-photon [Ca2+] imaging are performed in head-restrained mice while performing navigation in virtual reality to functionally characterize distinct pyramidal cells. This is followed by post hoc in vitro electrophysiological and anatomical experiments to reveal differences in intrinsic properties and synaptic innervation of the functionally characterized nerve cells.
ASD is a complex neurodevelopmental condition caused by interactions of environmental and genetic factors. Recently, maternal viral infections during pregnancy and their immunological consequences have received particular interest in research as risk factors for neurodevelopmental disorders.
In 2009 we described a novel form of modulation in the median raphe – hippocampus connection capable of selectively and rapidly recruiting a subset of inhibitory neurons. The function of this highly efficient form of modulation in shaping hippocampal representations is still unknown. In this project, we aim to unravel how the emergence and reorganization of hippocampal coding patterns linked to salient event is influenced by raphe-hippocampal rapid modulation.
Subcortical modulation is an indispensable component of cortical function, and ultimately, is key for adaptive behavioral responses. Therefore, disruption of subcortical modulation leads to debilitating psychiatric conditions. A key but largely ignored area of research concerns the control of subcortical modulation by cortical feedback. In this project we explore how the top-down control of the median raphe by the prefrontal cortex controls memory-guided behaviors. Our hope is to identify a missing link in the process that leads from normal subcortical function to pathological cortical operation.
Schizophrenia is a complex neurodevelopmental disorder that affects approximately 0.5%–1% of the global population and is 1 of the top 10 global causes of disability. Like most mental disorders, schizophrenia appears to be caused by a combination of genetic, environmental, and social risk factors linked to each other by epigenetic mechanisms regulating gene expression levels and molecular pathways. . Although the pathophysiology of schizophrenia is still not completely understood, there is a growing awareness that dysregulation of immune system components is fundamentally linked to the disorder.
Purinergic dysfunction are involved in the pathological process of mania and depression, but the essential association is not fully understood. The activation of the purinergic P2X7 receptor (P2X7R) plays a central role in inflammation, microglia activation and IL-1β release and activates NLRP3 inflammasome. We investigated whether the d-amphetamine (AMPH) has an inflammatory profile, and the P2X7R has an effect via IL-1β in this model.
Determining the location and density of various voltage- and ligand-gated ion channels in defined subcellular compartments of hippocampal pyramidal cells, using quantitative LM and EM immunolocalization. Perform multi-compartmental modeling to generate functionally testable predictions of the functional consequences of specialized ion channel distributions. In vitro electrophysiology and imaging approaches are used to test the functional predictions of our models.
Coding by transiently emerging co-active ensembles of neurons has long been a central tenet of neuroscience formulated in the influential assembly hypothesis. Accordingly, the animal’s actions can be predicted much more efficiently from the coordinated activity pattern of neurons than from the stimulus or event-locked spiking of single units. In contrast to cortical and hippocampal networks, assembly coding in subcortical modulatory circuits is almost fully unexplored. In this project, we aim to reveal and characterize the assembly code in the median raphe (MR), the source of ascending serotonergic neuromodulation of the limbic system. We expect to identify a fundamentally novel mode of neuromodulation whereby adaptive behavioral responses are controlled by the correlated activity of modulatory neuronal assemblies.
Determine the molecular specializations underlying the functional diversity of synapses, such as the probability and short-term plasticity of neurotransmitter release. In vitro electrophysiology, two-photon imaging, LM and EM immunolocalization are combined to address these issues.