Barron, H. | bioRxiv Science

bioRxiv2025

Synaptic histamine shapes the neurocomputational dynamics of human learning

Histamine was the first canonical monoamine identified in the mammalian brain 1-6, yet arguably remains the least understood in its mechanistic contributions to human behaviour. Using a first-in-class causal probe (H3R inverse agonist pitolisant), we show how increased synaptic histamine shapes offline and online temporal-hippocampal dynamics, sustaining learning-related activity and polarising retrieval computations. At a broader level, elevated histamine adaptively shifts neurocomputational strategy under high cognitive load, while stabilising value updates during aversive reinforcement learning. These findings uncover a mechanistically grounded influence of this underexplored system on human neurocomputation, supporting its therapeutic potential in psychiatry.

neuroscience↗

bioRxiv2017

Inhibitory Engrams In Perception And Memory.

Nervous systems use excitatory cell assemblies or \"perceptual engrams\" to encode and represent sensory percepts. Similarly, synaptically connected cell assemblies or \"memory engrams\" are thought to represent memories of past experience. Multiple lines of recent evidence indicate that brain systems also create inhibitory replicas of excitatory engrams with important cognitive functions. Such matched inhibitory engrams may form through homeostatic potentiation of inhibition onto postsynaptic cells that show increased levels of excitation. Inhibitory engrams can reduce behavioral responses to familiar stimuli thereby resulting in behavioral habituation. In addition, by preventing inappropriate activation of excitatory memory engrams, inhibitory engrams can make memories quiescent, stored in a latent form that is available for contextrelevant activation. In neural networks with balanced excitatory and inhibitory engrams, the release of innate responses and recall of associative memories can occur through focussed disinhibition. Understanding mechanisms that regulate the formation and expression of inhibitory engrams in vivo may help not only to explain key features of cognition, but also to provide insight into transdiagnostic traits associated with psychiatric conditions such as autism, schizophrenia and post-traumatic stress disorder (PTSD).

neuroscience↗