Biology subjects

Raudales, R.

Publications and source records attributed to Raudales, R..

6 recordsLinked to original sources

bioRxiv2025

Novel reactivity phenotype mediates long-term consequences of cocaine exposure during adolescence and adulthood in male Sprague-Dawley rats.

Individual differences in novelty seeking behavior often predict locomotor responses to psychomotor stimulants, an effect that may have a lasting impact throughout adolescence. The present study examined the role of novel reactivity phenotype on locomotor responses to repeated cocaine exposure during adolescence and adulthood in male rats. Prior to drug exposure, reactivity to a novel object was measured and animals were separated into low responders (LR) and high responders (HR). Cocaine was administered daily (0 or 20 mg/kg, i.p.) for 12 consecutive days, and behavior recorded on days 1, 6, and 12. After 28 days without drug, rats were challenged with cocaine (20 mg/kg) and behavior was assessed. Novel reactivity phenotype had a dramatic role in adolescents acute responsiveness to cocaine. HR adolescents exhibited a robust increase in sensitivity to acute administration of 20 mg/kg cocaine. However, following repeated cocaine exposure, both LR and HR adults displayed a marked increase in cocaine-induced locomotor activity, whereas the change in behavioral responsiveness in LR and HR adolescents was not as dramatic. During the cocaine challenge trial, LR that were exposed to 20 mg/kg cocaine during adolescence showed the highest cocaine-induced responsiveness compared to their saline-exposed and adult-exposed counterparts. Overall, these data indicate that novel reactivity phenotype and age of initial cocaine exposure are intricately involved in the long-term behavioral effects of cocaine. Thus, novel reactivity phenotype may predispose cocaine-using adolescents to continue drug-seeking behavior and potential abuse. HighlightsO_LINovel reactivity is higher in adolescents compared to adults C_LIO_LIAdolescents show greater acute cocaine-induced activity compared to adults C_LIO_LIHigh responding adolescents show robust acute cocaine-induced activity C_LIO_LILow responding adolescents show lasting changes in cocaine activity in adulthood C_LI

neuroscience↗

bioRxiv2024

Inhibition of striatal indirect pathway during second postnatal week leads to long lasting deficits in motivated behavior

Schizophrenia is a neuropsychiatric disorder with postulated neurodevelopmental etiology. Genetic and imaging studies have shown enhanced dopamine and D2 receptor occupancy in the striatum of patients with schizophrenia. However, whether alterations in postnatal striatal dopamine can lead to long lasting changes in brain function and behavior is still unclear. Here, we approximated striatal D2R hyperfunction in mice via designer receptor mediated activation of inhibitory Gi-protein signaling during a defined postnatal time window. We found that Gi-mediated inhibition of the indirect pathway during postnatal day 8-15 led to long lasting decreases in locomotor activity and motivated behavior measured in the adult animal. In vivo photometry further showed that the motivational deficit was associated with an attenuated adaptation of cue-evoked dopamine levels to changes in effort requirements. These data establish a sensitive time window of D2R-regulated striatal development with long lasting impacts on neuronal function and behavior.

animal behavior and cognition↗

bioRxiv2023

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons

Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remains poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage (Nkx2.1) and molecular (Unc5b, Pthlh) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.

neuroscience↗

bioRxiv2020

Genetic dissection of glutamatergic neuron subpopulations and developmental trajectories in the cerebral cortex

Diverse types of glutamatergic pyramidal neurons (PyNs) mediate the myriad processing streams and output channels of the cerebral cortex, yet all derive from neural progenitors of the embryonic dorsal telencephalon. Here, we establish genetic strategies and tools for dissecting and fate mapping PyN subpopulations based on their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target the temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable combinatorial targeting of major progenitor types and projection classes. Intersectional converter lines confer viral access to specific subsets defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of PyN subpopulations that assemble cortical processing networks and output channels.

neuroscience↗

bioRxiv2019

Multipotent radial glia progenitors and fate-restricted intermediate progenitors sequentially generate diverse cortical interneuron types

GABAergic interneurons deploy numerous inhibitory mechanisms that regulate cortical circuit operation, but the developmental programs that generate diverse interneuron types are not yet well understood. We carried out a comprehensive genetic fate mapping of the radial glial progenitors (RGs) and intermediate progenitors (IP) in the medial ganglionic eminence (MGE) in mice. We reveal that Nkx2.1+ RGs are multipotent and mediate two consecutive waves of neurogenesis, each sequentially generating different sets of interneuron types that laminate the neocortex in an inside-out-inside order. The first wave begins early and is restricted to the caudal MGE, has limited neurogenic window and capacity, and involves mostly apical IPs. The second wave begins later throughout the MGE, has an extended time course and large neurogenic capacity, and features a large set of fate-restricted basal IPs that amplify and diversify interneurons. Chandelier cells are generated toward the end of each wave and laminate in an outside-in order. Therefore, separate pools of multipotent RGs deploy temporal cohorts of IPs to sequentially generate diverse interneuron types.

neuroscience↗

bioRxiv2017

Transcriptional Architecture of Synaptic Communication Delineates Cortical GABAergic Neuron Identity

Understanding the organizational logic of neural circuits requires deciphering the biological basis of neuron type diversity and identity, but there is no consensus on defining a neuron type. We analyzed single cell transcriptomes of anatomically and physiologically characterized cortical ground truth populations and conducted a computational genomic screen for transcription profiles that distinguish them. We discovered that cardinal GABAergic neuron types are delineated by a transcriptional architecture that encodes their synaptic communication patterns. This architecture comprises 6 categories of ~40 gene families including cell adhesion molecules, transmitter-modulator receptors, ion channels, signaling proteins, neuropeptides and vesicular release components, and transcription factors. Combinatorial expression of select members across families shapes a multi-layered molecular scaffold along cell membrane that may customize synaptic connectivity patterns and input-output signaling properties. This molecular genetic framework of neuronal identity integrates cell phenotypes along multiple axes and provides a foundation for discovering and classifying neuron types.

neuroscience↗