Abstract
Coordinated activity patterns in the developing brain may contribute to the wiring of neuronal circuits underlying future behavioural requirements. However, causal evidence for this hypothesis has been difficult to obtain owing to the absence of tools for selective manipulation of oscillations during early development. We established a protocol that combines optogenetics with electrophysiological recordings from neonatal mice in vivo to elucidate the substrate of early network oscillations in the prefrontal cortex. We show that light-induced activation of layer II/III pyramidal neurons that are transfected by in utero electroporation with a high-efficiency channelrhodopsin drives frequency-specific spiking and boosts network oscillations within beta–gamma frequency range. By contrast, activation of layer V/VI pyramidal neurons causes nonspecific network activation. Thus, entrainment of neonatal prefrontal networks in fast rhythms relies on the activation of layer II/III pyramidal neurons. This approach used here may be useful for further interrogation of developing circuits, and their behavioural readout.
Highlights
Coordinated activity patterns in the developing brain may contribute to the wiring of neuronal circuits underlying future behavioural requirements
Viral vectors based on adeno-associated virus 8 or canine adenovirus that have been described as enabling fast (48 h–6 days) expression in vitro[29,30] led to insufficient, if any, expression of channelrhodopsins (ChRs) in the prelimbic subdivision (PL) of the prefrontal cortex (PFC) from P5–10 mice when injected in vivo 1–2 days after birth
Half-width of light-triggered action potentials (APs) was significantly reduced for layer II/III, but not for layer V/VI pyramidal cells (Figs 2e and 3e). To mechanistically explain these differences, we modelled the effect of Na þ /K þ conductances on the AP time course with the Hodgkin–Huxley model[39] (Supplementary Fig. 2)
Summary
Coordinated activity patterns in the developing brain may contribute to the wiring of neuronal circuits underlying future behavioural requirements. Pyramidal neurons and several classes of inhibitory interneurons dynamically interact to generate network activity in distinct frequency bands and enable diverse behaviours[11,12] Resolving these circuits by identifying the contribution of each neuronal population to the rhythmic network activity and overall brain function in vivo has been recently enabled by the development of technologies to control and manipulate neuronal activity at fast timescales[13,14]. Cell-type- and layer-specific transfection of neurons by in utero electroporation (IUE) was combined with head-fixed recordings of local field potential (LFP) and spiking activity in neonatal mice during light stimulation By these means we identified pyramidal neurons in layer II/III but not layer V/VI of the prelimbic subdivision (PL) of the prefrontal cortex (PFC) as key elements for the generation of beta–gamma oscillations during neonatal development
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