University of Cambridge > > Adrian Seminars in Neuroscience > How developmental origin determines microcircuit function in the hippocampus.

How developmental origin determines microcircuit function in the hippocampus.

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Most adult cortical dynamics are dominated by a minority of highly active neurons distributed within a silent neuronal mass. If cortical spikes are sparse, spiking of single distinct neurons can impact on network dynamics and drive an animal’s behavior. It is thus essential to understand whether this active and powerful minority is predetermined and if true to uncover the rules by which it is set during development. In this talk, I will present data supporting the possibility that birthdate is a critical determinant of neuronal network function into adulthood. More specifically, we reason that neurons that are born the earliest are primed to participate into adult network dynamics. This hypothesis is considerably fed by our past work aiming at understanding how cortical networks function and assemble during development. Hence, we have shown that an early birthdate: (1) specifies the specialization of GABA neurons with a hub function, that orchestrate perinatal network dynamics in the mouse hippocampus (Bonifazi et al. Science 2009) and develop into long-range projecting GABA neurons into adulthood (Picardo et al. Neuron 2011); (2) delineates a subtype of CA3 glutamate neuron with a “pacemaker” function in the absence of fast GAB Aergic transmission (Marissal et al. Nature Comm. 2012). I will first briefly present this set of published data. To test the hypothesis that early born cells are primed to be recruited in the active minority of neurons in the adult hippocampus, we needed to probe microcircuit function in vivo, where the extensive and long-range connectivity of these cells is preserved. I will show how we have translated from the in vitro to the in vivo situation, our multidisciplinary method to investigate structure-dynamics relationship in cortical networks. Using this approach, I will last present unpublished data showing that, in the absence of external landmarks, distance is encoded within the adult hippocampus in recurrent and self-circumscribed sequences of neuronal activation (Villette and Malvache et al., in revision). These sequences integrate traveled distance and link sequential body movements to an internal distance template. These distance sequences are an excellent theoretical and experimental model to probe the involvement of early born cells in sparse dynamics because they repeatedly involve small subsets of neurons and because they almost represent default hippocampal dynamics in the absence of any external drive, which is probably more likely to be influenced by developmental programs. In the future, we will examine the recruitment of early born neurons in this sparse hippocampal network dynamics pattern.

This talk is part of the Adrian Seminars in Neuroscience series.

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