Biology subjects

Pascual Garcia, M.

Publications and source records attributed to Pascual Garcia, M..

3 recordsLinked to original sources

bioRxiv2023

A minimum threshold for myelination of pyramidal cells in human and mouse neocortex

Neocortical pyramidal neurons are frequently myelinated. Diversity in the topography of axonal myelination in the cerebral cortex has been attributed to a combination of electrophysiological activity, axonal morphology, and neuronal-glial interactions. Previously, we showed that axonal segment length and calibre are critical determinants of fast-spiking interneuron myelination (Stedehouder, J. et al (2019). However, the factors that determine the myelination of individual axonal segments along neocortical pyramidal neurons remain largely unexplored. Here, we used structured illumination microscopy and cell type-specific manipulations to examine the extent to which axonal morphology determines the topography of axonal myelination in mouse neocortical pyramidal neurons. We found that, unlike what was determined for fast-spiking interneurons, the joint combination of axonal calibre and interbranch distance does not predict axonal myelination in pyramidal neurons, rather it provides a minimum threshold for myelination; pyramidal neurons with an axon calibre and interbranch distance lower than 0.24 {micro}m and 19 {micro}m, respectively, are almost never myelinated. Moreover, we further confirmed that these findings in mice also extend to human neocortical pyramidal cell myelination, suggesting that this mechanism is evolutionarily conserved. Taken together, our findings suggest that axonal morphology is highly deterministic of the topography and cell-type specificity of neocortical myelination.

neuroscience↗

bioRxiv2023

Dysfunctional parvalbumin interneurons in a genetic mouse model of schizophrenia

The 22q11 deletion syndrome (22q11DS) is an interstitial microdeletion associated to an increased risk of developing schizophrenia. In this disorder, there is a dysfunction in the overall connectivity of the brain. Parvalbumin-expressing (PV+) interneurons have been associated with multiple pre- and post-synaptic impairments that affect various brain regions. Specifically, previous results have suggested that alterations in hippocampal networks may be related to PV+ interneurons dysfunction. In this study, we used the Df1 mouse model that carries the 22q11 deletion to examine the excitability of PV+ cells in the dorsal CA1 region of the hippocampus, due to its importance in memory and cognition. We found that PV+ interneurons were hyperexcitable in this region. To understand the source of the altered excitability, we measured potassium currents, highly involved in the intrinsic firing properties of neurons. We observed that voltage-gated potassium channel subfamily A member 1 (Kv1.1) was impaired in PV+ cells. Specific activation of this channel recovered some of the excitability disturbances observed in Df1 mice. Furthermore, blockade of synaptic inputs also restored PV+ interneurons excitability. Taken together, these results suggest that PV excitability is increased in the CA1 region of the hippocampus and it is partially mediated by Kv1.1 in a mouse model of 22q11DS.

neuroscience↗

bioRxiv2023

A critical period for prefrontal cortex PV interneuron myelination and maturation

AbstractRecent studies have highlighted axonal myelination as a common feature of parvalbumin-positive (PV) interneurons throughout the cerebral cortex. However, the precise function of PV interneuron myelination remains incompletely understood. In this study, we used the cuprizone model of demyelination to investigate how PV interneuron myelination might influence their neuronal physiology. Specifically, we examined whether impairing myelination from postnatal day 21 onwards, during a critical neurodevelopmental period of the prefrontal cortex (PFC), can affect PV interneuron maturation and function. Using whole-cell patch-clamp recordings to examine intrinsic properties of PV interneurons in the PFC, we found that juvenile demyelination induced robust alterations of PV interneuron firing patterns. Specifically, we observed that demyelination caused an impairment in the ability of PV interneurons to sustain high frequency firing associated with a substantial decrease in Kv3-specific currents. We also found a significant impairment in PV interneuron autaptic self-inhibitory transmission, a feature implicated in temporal control of PV interneuron firing during cortical network activity. Following a remyelination period of 5 weeks, PV interneuron properties were only partially recovered and mice showed clear social deficits, suggesting that transient juvenile demyelination leads to long-lasting behavioral impairments. In contrast, adult demyelination had no significant effects on PV interneuron firing properties. Together, our data uncovers a critical period for juvenile myelination as an important factor in PFC PV interneuron development and brain maturation.

neuroscience↗