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EJN Video (ID 6183)
The synaptome: an epic journey in time and space (ID 1281)
There are around a million billion synapses in the human brain, with each containing hundreds of thousands of proteins that are encoded by over a thousand genes. The differential distribution of these proteins generates a vast and potentially unlimited synapse diversity. The different types of synapses are spatially organised across dendrites, neurons, brain regions and at the global systems level into the ‘synaptome architecture’ of the brain. This synaptome architecture is initially very simple at birth, but during childhood an explosion of synapse diversity increases its complexity, reaching a zenith in young adults. Synaptome architecture indeed changes at all ages and undergoes a trajectory that parallels the lifespan trajectory of cognitive function. Synapse diversity allows synapses in particular locations to preferentially respond to some patterns of activity, thereby providing a way of storing and retrieving behavioural representations. Surprisingly, much of the synaptic molecular machinery arose in unicellular organisms, 3 billion years before the brain, where it controlled the behavioural repertoire. Thus, the protein machinery of synapses has been a conserved behavioural mechanism across many phyla and much evolutionary time. The mechanisms that build the synaptome are targeted by mutations causing over 100 brain diseases and by experience, drugs, brain injury and neuroinflammation.
Prefrontal circuits for decision making (ID 1298)
During primate evolution, prefrontal cortex (PFC) expanded substantially relative to other cortical areas. The expansion of PFC circuits likely supported the increased cognitive abilities of humans and anthropoids to plan, evaluate, and decide between different courses of action. But what do PFC circuits compute as a decision is being made? To address this, we recorded time-varying PFC activity during value-based decision making, using single unit recording in non-human primates and magnetoencephalography in humans. At a macrocircuit level, we found that value correlates differ substantially across PFC subregions. They are heavily shaped by each subregion’s anatomical connections and by the decision-maker’s current locus of attention. At a microcircuit level, we found that the temporal evolution of value correlates can be predicted using cortical recurrent network models that temporally integrate incoming decision evidence. These models mirror recent work in cognitive psychology, describing human economic decision making as a process of attention-weighted evidence integration across time.