Neves, R. M. | Search bioRxiv

bioRxiv2020

Intraneuronal chloride accumulation via NKCC1 is not essential for hippocampal network development in vivo

NKCC1 is the primary transporter mediating chloride uptake in immature principal neurons, but its role in the development of in vivo network dynamics and cognitive abilities remains unknown. Here, we address the function of NKCC1 in developing mice using electrophysiological, optical and behavioral approaches. We report that NKCC1 deletion from telencephalic glutamatergic neurons decreases in-vitro excitatory GABA actions and impairs neuronal synchrony in neonatal hippocampal brain slices. In vivo, it has a minor impact on correlated spontaneous activity in the hippocampus and does not affect network activity in the intact visual cortex. Moreover, long-term effects of the developmental NKCC1 deletion on synaptic maturation, network dynamics and behavioral performance are subtle. Our data reveal a neural network function of depolarizing GABA in the hippocampus in vivo, but challenge the hypothesis that NKCC1 is essential for major aspects of hippocampal development.

neuroscience↗

bioRxiv2017

Monitoring large populations of locus coeruleus neurons reveals the non-global nature of the norepinephrine neuromodulatory system

Understanding the forebrain neuromodulation by the noradrenergic locus coeruleus (LC) is fundamental for cognitive and systems neuroscience. The diffuse projections of individual LC neurons and presumably their synchronous spiking have long been perceived as features of the global nature of noradrenergic neuromodulation. Yet, the commonly referenced \"synchrony\" underlying global neuromodulation, has never been assessed in a large population, nor has it been related to projection target specificity. Here, we recorded up to 52 single units simultaneously (3164 unit pairs in total) in rat LC and characterized projections by stimulating 15 forebrain sites. Spike count correlations were low and, surprisingly, only 13% of pairwise spike trains had synchronized spontaneous discharge. Notably, even noxious sensory stimulation did not activate the entire population, only evoking synchronized responses in ~16% of units on each trial. We also identified novel infra-slow (0.01-1 Hz) fluctuations of LC unit spiking that were asynchronous across the population. A minority, synchronized possibly by gap junctions, was biased toward restricted (non-global) forebrain projection patterns. Finally, we characterized two types of LC single units differing by waveform shape, propensity for synchronization, and interactions with cortex. These cell types formed finely-structured ensembles. Our findings suggest that the LC conveys a highly complex, differentiated, and potentially target-specific neuromodulatory signal.

neuroscience↗