Biology subjects

Ghezzi, F.

Publications and source records attributed to Ghezzi, F..

3 recordsLinked to original sources

bioRxiv2020

Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

Development of the cortical circuits for sensory-motor processing require the coordinated integration of both columnar and long-range synaptic connections. To understand how this occurs at the level of individual neurons we have explored the timeline over which vasoactive intestinal peptide (VIP)-expressing interneurons integrate into mouse somatosensory cortex. We find a distinction in emergent long-range anterior-motor and columnar glutamatergic inputs onto layer (L)2 and L3 VIP+ interneurons respectively. In parallel, VIP+ interneurons form efferent connections onto both pyramidal cells and interneurons in the immediate column in an inside-out manner. Cell-autonomous deletion of the fate-determinant transcription factor, Prox1, spares long-range anterior-motor inputs onto VIP+ interneurons, but leads to deficits in local connectivity. This imbalance in the somatosensory circuit results in altered spontaneous and sensory-evoked cortical activity in vivo. This identifies a critical role for VIP+ interneurons, and more broadly interneuron heterogeneity, in formative circuits of neocortex.

neuroscience↗

bioRxiv2020

Non-canonical role for Lpar1-EGFP subplate neurons in early postnatal somatosensory cortex

Subplate neurons (SPNs) are a transient neuronal population shown to play a key role in nascent sensory processing relaying thalamic information to the developing cerebral cortex. However there is little understanding of how heterogeneity within this population relates to emergent function. To address this question we employed optical and electrophysiological technologies to investigate the synaptic connectivity of SPNs defined by expression of the Lpar1-EGFP transgene through the first postnatal week in primary whisker somatosensory cortex (S1BF) in mouse. Our data identify that the Lpar1-EGFP SPNs represent two morphological subtypes: (1) transient, fusiform SPNs with axons largely restricted to the subplate zone; (2) pyramidal SPNs with axon collaterals that traverse the overlying cortex to extend through the marginal zone. Laser scanning photostimulation of caged glutamate was used to determine columnar glutamatergic and GABAergic input onto both of these SPN subtypes. These experiments revealed that the former receive translaminar input from more superficial cortical layers up until the emergence of the whisker barrels (~postnatal (P)5). In contrast, pyramidal SPNs only receive local input from the adjacent subplate network at early ages but then at later ages can acquire varied input from the overlying cortex. Combined electrical stimulation of the ventral posterior nucleus of the thalamus and optogenetic activation of thalamic afferents in thalamocortical slice preparations revealed that Lpar1-EGFP SPNs only receive sparse thalamic innervation during early postnatal development. Taken together, these data reveal two components of the postnatal network that interpret sparse thalamic input to direct the emergent columnar structure of neonatal somatosensory cortex.

neuroscience↗

bioRxiv2020

Average beta burst duration profiles provide a signature of dynamical changes between the ON and OFF medication states in Parkinson's disease

Parkinsons disease motor symptoms are associated with an increase in subthalamic nucleus beta band oscillatory power. However, these oscillations are phasic, and there is a growing body of evidence suggesting that beta burst duration may be of critical importance to motor symptoms. This makes insights into the dynamics of beta bursting generation valuable, in particular to refine closed-loop deep brain stimulation in Parkinsons disease. In this study, we ask the question "Can average burst duration reveal how dynamics change between the ON and OFF medication states?". Our analysis of local field potentials from the subthalamic nucleus demonstrates using linear surrogates that the system generating beta oscillations is more likely to act in a non-linear regime OFF medication and that the change in a non-linearity measure is correlated with motor impairment. In addition, we pinpoint the simplest dynamical changes that could be responsible for changes in the temporal patterning of beta oscillations between medication states by fitting to data biologically inspired models, and simpler beta envelope models. Finally, we show that the non-linearity can be directly extracted from average burst duration profiles under the assumption of constant noise in envelope models. This reveals that average burst duration profiles provide a window into burst dynamics, which may underlie the success of burst duration as a biomarker. In summary, we demonstrate a relationship between average burst duration profiles, dynamics of the system generating beta oscillations, and motor impairment, which puts us in a better position to understand the pathology and improve therapies such as deep brain stimulation. Author summaryIn Parkinsons disease, motor impairment is associated with abnormal oscillatory activity of neurons in deep motor regions of the brain. These oscillations come in the shape of bursts, and the duration of these bursts has recently been shown to be of importance to motor symptoms. To better understand the disease and refine therapies, we relate the duration of these bursts to properties of the system generating them in the pathological state and in a proxy of the healthy state. The data suggest that the system generating bursts involves more complexity in the pathological state, and we show that a measure of this complexity is associated with motor impairment. We propose biologically inspired models and simpler models that can generate the burst patterns observed in the pathological and healthy state. The models confirm what was observed in data, and tell us how burst generation mechanisms could differ in the disease. Finally, we identify a mathematical link allowing us to infer properties of the burst generating system from burst duration measurements in patient recordings. This sheds some light on the significance of burst duration as a marker of pathology.

neuroscience↗