Past events

<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>

The role of neurons in the direction-selective retinal circuit in visual processing in the retina and in the visual thalamus The lateral geniculate nucleus (LGN) of the thalamus is a major retinal target, involved in processing and relaying visual information, including direction selectivity (DS) and orientation selectivity (OS). How DS and OS are organized in the LGN is poorly understood, as well as whether this information is directly inherited from the retina or generated de novo within the LGN. Using extracellular recordings from across the mouse LGN, we studied DS and OS responses and their topographic organization. We found that DS responses are absent in the central visual field, and that their preferred directions are topographically aligned to match translational optic flow patterns in the remaining visual field. OS responses were uniformly distributed throughout the visual field. By eliminating retinal DS in transgenic mice, we found that DS- but not OS-responses in the LGN were dependent on retinal DS. Thus, LGN DS is inherited from the retina, but retinogeniculate transfer may be topography-dependent, optimizing representations that support visually-guided behaviors.

While cognitive neuroscientists have uncovered principles of perceptual decision-making by analyzing choices and neuronal firing across thousands of trials, we do not yet know the behavioral or neuronal dynamics underlying one SINGLE choice. For instance, why might a subject judge a given stimulus in category A 70% of the time but in category B 30%? Until we can work out precisely what determines single-decisions – this choice, right now – the mechanisms of real-world decision-making will remain unknown. In tactile psychophysical tasks with rats and humans, we are trying to sort out factors that explain the variability in judgments (across trials) to the identical stimulus input. We identify four factors: (i) trial-to-trial fluctuations in sensory coding, (ii) temporal context, namely, the history of preceding stimuli and choices, (iii) attention, and (iv) bias (predictions originating in beliefs about the environment’s probabilistic structure). The strategy is to bring these factors under experimental control, rather than leaving them to vary according to uninterrogated states within the subject. Psychophysics from rats and humans show that large chunks of variability are accounted for by these factors; evidence from cortical neuronal populations in rats provides some mechanistic grounding.

<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>

The role of neurons in the direction-selective retinal circuit in visual processing in the retina and in the visual thalamus The lateral geniculate nucleus (LGN) of the thalamus is a major retinal target, involved in processing and relaying visual information, including direction selectivity (DS) and orientation selectivity (OS). How DS and OS are organized in the LGN is poorly understood, as well as whether this information is directly inherited from the retina or generated de novo within the LGN. Using extracellular recordings from across the mouse LGN, we studied DS and OS responses and their topographic organization. We found that DS responses are absent in the central visual field, and that their preferred directions are topographically aligned to match translational optic flow patterns in the remaining visual field. OS responses were uniformly distributed throughout the visual field. By eliminating retinal DS in transgenic mice, we found that DS- but not OS-responses in the LGN were dependent on retinal DS. Thus, LGN DS is inherited from the retina, but retinogeniculate transfer may be topography-dependent, optimizing representations that support visually-guided behaviors.

While cognitive neuroscientists have uncovered principles of perceptual decision-making by analyzing choices and neuronal firing across thousands of trials, we do not yet know the behavioral or neuronal dynamics underlying one SINGLE choice. For instance, why might a subject judge a given stimulus in category A 70% of the time but in category B 30%? Until we can work out precisely what determines single-decisions – this choice, right now – the mechanisms of real-world decision-making will remain unknown. In tactile psychophysical tasks with rats and humans, we are trying to sort out factors that explain the variability in judgments (across trials) to the identical stimulus input. We identify four factors: (i) trial-to-trial fluctuations in sensory coding, (ii) temporal context, namely, the history of preceding stimuli and choices, (iii) attention, and (iv) bias (predictions originating in beliefs about the environment’s probabilistic structure). The strategy is to bring these factors under experimental control, rather than leaving them to vary according to uninterrogated states within the subject. Psychophysics from rats and humans show that large chunks of variability are accounted for by these factors; evidence from cortical neuronal populations in rats provides some mechanistic grounding.