Biology subjects

Rodriguez-Contreras, A.

Publications and source records attributed to Rodriguez-Contreras, A..

4 recordsLinked to original sources

bioRxiv2022

The general anesthetic isoflurane inhibits calcium activity in cerebrovascular endothelial cells and disrupts vascular tone

Calcium signaling in cerebrovascular endothelial cells (CVECs) has been identified to play key physiological and pathological roles in blood brain barrier function and neurovascular coupling, which involve dynamic changes in vessel diameter. However, there are no studies that measured correlated changes in vessel diameter and calcium activity in CVECs in vivo. In this study, we used the general anesthetic isoflurane (ISO) to induce a maximally dilated state in cortical blood vessels and measured the effects of the manipulation on CVEC calcium reporter activity in awake Cdh5BAC-GCaMP mice by use of two-photon fluorescence microscopy through thinned skull cranial windows. For the first time, we report dual effects of ISO on calcium activity in cerebral blood vessels of different diameter. During anesthesia induction ISO exposure triggered a short latency synchronous increase in calcium activity, followed by a period of activity suppression in small, medium, and large diameter vessels. Furthermore, during anesthesia maintenance calcium activity was desynchronized, and the relationship between vascular tone and calcium activity was disrupted in all vessel types. Based on these results we propose that there is a feedback mechanism between intracellular calcium fluctuations in CVECs and the maintenance of cerebrovascular tone.

neuroscience↗

bioRxiv2021

Characterization of developmental changes in spontaneous electrical activity of superior olivary neurons before hearing onset under injectable or volatile anesthesia

In this work we studied the impact of two widely used anesthetics on the electrical activity of auditory brainstem neurons during development. The spontaneous electrical activity in neonate rats of either sex was analyzed under the injectable mix of ketamine/xylazine (K/X mix) and the volatile anesthetic isoflurane (ISO). We used a ventral craniotomy in mechanically ventilated pups to carry out electrophysiology recordings in the superior olivary complex (SOC) between birth (postnatal day 0, P0) and P12. To characterize neuronal activity of single and ensembles of neurons, we performed patch clamp and multi-electrode experiments under different anesthetic conditions. Our results provide the first study that compares K/X mix and ISO in the same rodent species. We demonstrate that electrical activity of SOC neurons ramps up during development, and that the firing pattern of single units recorded in K/X mix was similar to that reported in ISO anesthetized rat pups. However, ISO displayed a large scatter on its suppressing effects on electrical activity when delivered at 1.5% in the presence or the absence of K/X mix. Taken together, our results shed light on the use of anesthetics for future studies to enable electrophysiology or optical imaging studies in-vivo to obtain functional information on the activity of medial olivochoclear neurons and their role in auditory development.

neuroscience↗

bioRxiv2020

Robust range of auditory periphery development, eye opening, and brain gene expression in Wistar rat pups that experience variation in maternal backgrounds

The experience of variation in maternal licking and grooming (LG) is considered a critical influence in neurodevelopment related to stress and cognition, but little is known about its relationship to early sensory development. In this study, we used a maternal selection approach to test the hypothesis that differences in LG during the first week of life influence the timing of hearing onset in Wistar rat pups. We performed a range of tests, including auditory brainstem responses (ABR), tracking of eye opening (EO), micro-CT X-ray tomography, and qRT-PCR to monitor neurodevelopmental changes in the female and male progeny of low-LG and high-LG dams. Our results show that variation in maternal LG is not overtly associated with different timing of ABR onset and EO in the progeny. However, the data provide insight on the delay between hearing onset and EO, on key functional and structural properties that define hearing onset at the auditory periphery, and on changes in brain gene expression that include the first evidence that: a) the hypoxia-sensitive pathway is regulated in subcortical and cortical auditory brain regions before hearing onset, and b) implicates maternal LG in regulation of Bdnf signaling in auditory cortex after hearing onset. Altogether, these findings provide a baseline to evaluate how factors that severely disrupt the early maternal environment may affect the expression of robust developmental sensory programs. SIGNIFICANCE STATEMENTEarly life experience during sensitive developmental periods can induce long-term effects on the neurobiological development of the offspring. In the present work we tested the hypothesis that variation in maternal licking and grooming (LG) affects the timing of hearing onset in Wistar rat pups. To our surprise the results did not support the hypothesis. Instead, we found a robust range of early and late auditory development that was independent of maternal LG. Nevertheless, the study provides new findings on the delay between hearing onset and eye opening, on key functional and structural properties that define hearing onset at the auditory periphery, and the first evidence that a) the hypoxia-sensitive pathway is regulated in the central auditory system during the sensitive period before hearing onset, and b) maternal LG is implicated in regulation of Bdnf signaling during the sensitive period after hearing onset. These findings provide a baseline to evaluate how factors that severely disrupt the early maternal environment may affect the expression of robust developmental sensory programs.

neuroscience↗

bioRxiv2018

Strengthening of the efferent olivocochlear system leads to synaptic dysfunction and tonotopy disruption of a central auditory nucleus

The auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an 9 cholinergic receptor knock-in mouse model (of either sex) with enhanced medial efferent activity (Chrna9L9T, L9T) to understand the role of the olivocochlear system in the correct establishment of auditory circuits. Wave III of auditory brainstem responses (which represents synchronized activity of synapses within the superior olivary complex) were smaller in L9T mice, suggesting a central dysfunction. The mechanism underlying this functional alteration was analysed in brain slices containing the medial nucleus of the trapezoid body (MNTB), where neurons are topographically organized along a medio-lateral axis. The topographic organization of MNTB physiological properties observed in WT mice was abolished in the L9T mice. Additionally, electrophysiological recordings in slices evidenced MNTB synaptic alterations, which were further supported by morphological alterations. The present results suggest that the transient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement of topographic maps as well as in setting the correct synaptic transmission at central auditory nuclei.\n\nSignificance StatementCochlear inner hair cells of altricial mammals display spontaneous electrical activity before hearing onset. The pattern and firing rate of these cells is crucial for the correct maturation of the central auditory pathway. A descending efferent innervation from the central nervous system contacts hair cells during this developmental window. The function of this transient efferent innervation remains an open question. The present work shows that the genetic enhancement of efferent function disrupts the orderly topographic distribution at the medial nucleus of the trapezoid body level and causes severe synaptic dysfunction. Thus, the transient efferent innervation to the cochlea is necessary for the correct establishment of the central auditory circuitry.

neuroscience↗