Past events

<p>Animal tract-tracing studies provided critical insights into the organizational principles of the hippocampal system, thus defining the anatomical constraints within which animal mnemonic functions operate. However, no clear framework defining the anatomical organization of the human hippocampal system exists. This gap in knowledge originates in notoriously low MRI data quality in the human medial temporal lobe (MTL) and in group-level blurring of idiosyncratic anatomy between adjacent brain regions comprising the MTL. In this talk, I will present our recent data, which overcame these longstanding challenges and allowed us to explore in detail the cortical networks associated with the human MTL, and to examine the intrinsic organization of the hippocampal-entorhinal system with unprecedented anatomical precision. Our results point to biologically meaningful and previously unknown organizational principles of the human hippocampal system. These findings facilitate the study of the evolutionary trajectory of the hippocampal connectivity and function across species, and prompt a reformulation of the neuroanatomical basis of episodic memory.</p>

<p>How do animals make perceptual decisions about sensory stimuli to guide motor actions? One hypothesis is that dedicated "perceptual decision" cells process sensory information and drive the appropriate action. Alternatively, perceptual decisions result from competition among cells driving different actions, making decisions inherently coupled to actions. To distinguish between these hypotheses, we designed a vibrotactile detection task in which mice flexibly switched between standard and reversed contingency blocks, respectively requiring them to lick after stimulus presence or absence. Optogenetic inactivation of somatosensory and secondary motor cortices reduced stimulus sensitivity without impairing the ability to lick. However, widefield and two-photon imaging found that differences in cortical activity across perceptual decisions were almost exclusively action-coupled. In addition, we identified a subset of cells that encoded the current contingency block in a gated manner, enabling mice to flexibly make decisions without relying on action-independent decision coding.</p>

<p>The brain can form associations between sensory information of inner and/or outer world (e.g. Pavlovian conditioning) but also between sensory information and the immune system. The phenomenon which was described in the last century is termed conditioned immune response (CIR) but very little is known about neuronal mechanisms subserving it.&nbsp; The conditioned stimulus can be a given taste and the unconditioned stimulus is an agent that induces or reduces a specific immune response.&nbsp; Over the last years, we and others revealed molecular and cellular mechanisms underlying taste valance representation in the anterior insular cortex (aIC). Recently, a circuit in the posterior insular cortex (pIC) encoding the internal representation of a given immune response was identified. Together, it allowed us to hypothesize and prove that the internal reciprocal connections between the anterior and posterior insula encode CIR.&nbsp; One can look at CIR as a noon declarative form of Nocebo effect and thus we demonstrate for the first time a detailed circuit mechanism for Placebo/Nocebo effect in the cortex.</p>

<p>Traumatic brain (TBI) injuries result in profound local hypoperfusion, ischemia, chronic inflammation and refractory seizures(post-traumatic epilepsy (PTE)), and restrict drug delivery to the site of impact so that peripheral treatment alone would have limited access to the site of injury during the most critical phases of neurotrauma. Cannabidiol (CBD), the major non-psychotropic cannabinoid, has anti-convulsant, anti-inflammatory, anti-nociceptive, antioxidant, and immuno-suppressive properties not fully understood. In pre-juvenile rats, microinjection of CBD attenuated kainate(KA)-induced seizures to a greater extent than intraperitoneal injection, indicating that local drug administration was more effective. In adult rats after experimental TBI, our modified CBD-infused implant applied extradural with oil injection supplementation restored vestibulomotorand cognitive functions compared to systemic treatment alone. We questioned whether the CBD or the low concentrations of THC in the extract was responsible for behavioral and cellular recovery.We hypothesized that an optimal ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) is required to protect against neuropathological consequences following TBI greater than either substance alone. Varied CBD:THC extract concentrations were compared with hempCBD lacking THC (CBD0). Neurons, glia, and parvalbumin interneurons (PV-INs) were evaluated. Weight loss was observed following high doses of THC dominant cannabis, THC100:1. Neuroscoresand vestibulomotorperformance were restored more with CBD:THC300:1-10:1. However, THC dominant treatments resulted in early onset to spontaneous seizures post-TBI. In a non-reward T-maze, the CBD10:1group had the highest alternation rates; TBI + vehicle, CBD0, CBD1:1, and THC100:1treatment groups had the lowest. The novel object recognition memory task showed CBD300:1treated animals had the best performance, while TBI or THC100:1treated groups had the worst. The forced swim test (FST) showed immobility time was highest after TBI and lowest after THC100:1treatment. The elevated plus maze (EPM) revealed the CBD0group spent the most time in closed arms. Both tests indicate that reduced anxiety was THC dependent. All combinations resulted in reduced injury but CBD10:1and THC20:1gave the most protection and THC100:1the least. Reduced anxiety level was THC dependent but higher doses were pro-convulsant cautioning THC dosing. Reduced GFAP labeling was highest with CBD dominant cannabis supporting its neuroprotective role against inflammation. Rescue of diminished bilateral PV-INs was observed within the hippocampus and medial prefrontal cortex (mPFC) with CBD dominant treatment (CBD300, CBD0) supporting their anticonvulsant effect. Loss of PV-INs with THC dominant treatment supports their proconvulsant effect. Thus, CBD and THC have different beneficial therapeutic effects indicating an optimal concentration ratio is critical for optimal neuropathological therapeutics.</p><p>Light refreshments before the seminar</p>