Abstract |
Working memory refers to the temporary storage of information and is strongly associated with the prefrontal cortex (PFC). Persistent activity of cortical neurons, namely the activity that persists beyond the stimulus presentation, is considered the cellular correlate of working memory. Although past studies suggested that this type of activity is characteristic of large scale networks, recent experimental evidence imply that small, tightly interconnected clusters of neurons in the cortex may support similar functionalities. In addition, very little is known about the biophysical mechanisms giving rise to persistent activity in small-sized microcircuits in the PFC. In this work, we developed biophysically detailed microcircuit models of morphologically simplified or detailed layer 5 PFC neurons that incorporated connectivity constraints and were validated against a multitude of experimental data. We used this microcircuit model to study the mechanisms that support persistent activity in a realistic framework. Our results show that PFC microcircuits can serve as tunable modules for persistent activity induction. We show that the underlying mechanisms are different when investigated in large-scaled compared to small-scaled networks: in microcircuits, persistent activity strongly depends on dendritic non-linearities and is shaped by the morphological properties of the basal dendrites, providing a link between dendritic morphology and neuronal function. Overall, this study zooms out from dendrites to cell assemblies and suggests a tight interaction between dendritic non-linearities, morphology and network properties that may facilitate the short-term memory function of the PFC. Our model generates a number of experimentally testable predictions that may lead to a better understanding of the physiological and pathological function of prefrontal cortex.
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