Fear learning induces synaptic potentiation between engram neurons in the rat lateral amygdala
Fear learning induces synaptic potentiation between engram neurons in the rat lateral amygdala. This study by Marios Abatis et al. demonstrates how fear conditioning strengthens synaptic connections between engram cells in the lateral amygdala, revealed through optogenetic identification of neuronal ensembles and electrophysiological measurements. The work provides crucial insights into memory formation mechanisms at the synaptic level, with implications for understanding anxiety disorders and developing targeted interventions. Presented by Dr. Kenneth Hayworth, this journal club will explore the paper's methodology linking engram cell reactivation with synaptic plasticity measurements, and discuss implications for memory decoding research.
Memory formation in hippocampal microcircuit
The centre of memory is the medial temporal lobe (MTL) and especially the hippocampus. In our research, a more flexible brain-inspired computational microcircuit of the CA1 region of the mammalian hippocampus was upgraded and used to examine how information retrieval could be affected under different conditions. Six models (1-6) were created by modulating different excitatory and inhibitory pathways. The results showed that the increase in the strength of the feedforward excitation was the most effective way to recall memories. In other words, that allows the system to access stored memories more accurately.
How dendrites help solve biological and machine learning problems
Dendrites are thin processes that extend from the cell body of neurons, the main computing units of the brain. The role of dendrites in complex brain functions has been investigated for several decades, yet their direct involvement in key behaviors such as for example sensory perception has only recently been established. In my presentation I will discuss how computational modelling has helped us illuminate dendritic function. I will present the main findings of a number of projects in lab dealing with dendritic nonlinearities in excitatory and inhibitory and their consequences on neuronal tuning and memory formation, the role of dendrites in solving nonlinear problems in human neurons and recent efforts to advance machine learning algorithms by adopting dendritic features.
New Strategies and Approaches to Tackle and Understand Neurological Disorder
Broadly, the Mauro Costa-Mattioli laboratory (The MCM Lab) encompasses two complementary lines of research. The first one, more traditional but very important, aims at unraveling the molecular mechanisms underlying memory formation (e.g., using state-of-the-art molecular and cell-specific genetic approaches). Learning and memory disorders can strike the brain during development (e.g., Autism Spectrum Disorders and Down Syndrome), as well as during adulthood (e.g., Alzheimer’s disease). We are interested in understanding the specific circuits and molecular pathways that are primarily targeted in these disorders and how they can be restored. To tackle these questions, we use a multidisciplinary, convergent and cross-species approach that combines mouse and fly genetics, molecular biology, electrophysiology, stem cell biology, optogenetics and behavioral techniques. The second line of research, more recent and relatively unexplored, is focused on understanding how gut microbes control CNS driven-behavior and brain function. Our recent discoveries, that microbes in the gut could modulate brain function and behavior in a very powerful way, have added a whole new dimension to the classic view of how complex behaviors are controlled. The unexpected findings have opened new avenues of study for us and are currently driving my lab to answer a host of new and very interesting questions: - What are the gut microbes (and metabolites) that regulate CNS-driven behaviors? Would it be possible to develop an unbiased screening method to identify specific microbes that regulate different behaviors? - If this is the case, can we identify how members of the gut microbiome (and their metabolites) mechanistically influence brain function? - What is the communication channel between the gut microbiota and the brain? Do different gut microbes use different ways to interact with the brain? - Could disruption of the gut microbial ecology cause neurodevelopmental dysfunction? If so, what is the impact of disruption in young and adult animals? - More importantly, could specific restoration of selected bacterial strains (new generation probiotics) represent a novel therapeutic approach for the targeted treatment of neurodevelopmental disorders? - Finally, can we develop microbiota-directed therapeutic foods to repair brain dysfunction in a variety of neurological disorders?
Cellular mechanisms of conscious perception
Arguably one of the biggest mysteries in neuroscience is how the brain stores long-term memories. The major challenge for investigating the neural circuit underlying memory formation in the neocortex is the distributed nature of the resulting memory trace throughout the cortex. Here, we used a new behavioral paradigm that enabled us to generate memory traces in a specific cortical location and to specifically examine the mechanisms of memory formation in that region. We found that medial-temporal inputs arrive in neocortical layer 1 where the apical dendrites of cortical pyramidal neurons predominate. These dendrites have active properties that make them sensitive to contextual inputs from other areas that also send axons to layer 1 around the cortex. Blocking the influence of these medial-temporal inputs prevented learning and suppressed resulting dendritic activity. We conclude that layer 1 is the locus for hippocampal-dependent memory formation in the neocortex and propose that this process enhances the sensitivity of the tuft dendrites to contextual inputs.
Hippocampal replays appear after a single experience and slow down with subsequent experience as greater detail is incorporated
The hippocampus is implicated in memory formation, and neurons in the hippocampus take part in replay sequences, time-compressed reactivations of trajectories through space the animal has previously explored. These replay sequences have been proposed to be a form of memory for previously experienced places. I will present work exploring how these replays appear and change with experience. By recording from large ensembles of hippocampal neurons as rats explored novel and familiar linear tracks in various experiments, we found that hippocampal replays appear after a single experience and slow down with subsequent experience as greater detail is incorporated. We also investigated hover-and-jump dynamics within replays that are associated with the slow gamma (25-50Hz) oscillation in the LFP and found that replays slow down by adding more hover locations, corresponding to depiction of the behavioral trajectory with increased resolution. Thus, replays can reflect single experiences, and be rapidly modified by subsequent experience to incorporate more detail, consistent with their proposed role as a basic mechanism of hippocampally dependent memory.
The recruitment of spatial cells in large-scale space & an AI approach to neural discovery
Prof Caswell Barry, Professorial Research Fellow, Cell & Developmental Biology, Division of Biosciences, University College London. He and his team are trying to understand how the brain works - how it creates that experience of being human, and more specifically, how the brain creates, stores, and updates memories for places and events. They are trying to answer this is by studying areas of the brain linked to memory, the hippocampus and associated sections of cortex – by recording the activity of neurons in these areas we can visualise and hopefully understand the processes the trigger memory formation and retrieval.