Biology subjects

Turrero Garcia, M.

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

6 recordsLinked to original sources

bioRxiv2024

Conservation, alteration, and redistribution of mammalian striatal interneurons

Mammalian brains vary in size, structure, and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved1-4. Recent studies suggest there is a primate-specific population of striatal inhibitory interneurons, the TAC3 interneurons5. However, there has not yet been a detailed analysis of the spatial and phylogenetic distribution of this population. Here, we profile single cell gene expression in the developing pig (an ungulate) and ferret (a carnivore), representing 94 million years divergence from primates, and assign newborn inhibitory neurons to initial classes first specified during development6. We find that the initial class of TAC3 interneurons represents an ancestral striatal population that is also deployed towards the cortex in pig and ferret. In adult mouse, we uncover a rare population expressing Tac2, the ortholog of TAC3, in ventromedial striatum, prompting a reexamination of developing mouse striatal interneuron initial classes by targeted enrichment of their precursors. We conclude that the TAC3 interneuron initial class is conserved across Boreoeutherian mammals, with the mouse population representing Th striatal interneurons, a subset of which expresses Tac2. This study suggests that initial classes of telencephalic inhibitory neurons are largely conserved and that during evolution, neuronal types in the mammalian brain change through redistribution and fate refinement, rather than by derivation of novel precursors early in development.

evolutionary biology↗

bioRxiv2024

Multimodal classification of neurons in the lateral septum

The lateral septum (LS) is a ventral forebrain nucleus that modulates complex social and affective behaviors. These behaviors emerge from heterogeneous neuronal populations whose molecular identity and developmental origins remain poorly defined. We profiled the transcriptional identity of mature LS neurons derived from two progenitor lineages distinguished by their embryonic origin and Nkx2.1 expression history, identifying 22 molecularly distinct subtypes. Nkx2.1-lineage neurons are enriched for select cell adhesion and communication molecules; however, subtypes from distinct developmental origins can converge onto similar molecular profiles when residing within the same LS subregion. The graded expression of genes related to synaptic signaling is a primary axis defining the taxonomy of LS neurons. Using transcriptional markers, we labeled non-overlapping neuronal populations and characterized their connectivity, morphology, and electrophysiology. Together, these findings define the extent of LS neuronal diversity and provide a framework for understanding how complex behaviors are regulated by the LS.

neuroscience↗

bioRxiv2023

A developmentally defined population of neurons in the lateral septum controls responses to aversive stimuli

When interacting with their environment, animals must balance exploratory and defensive behavior to evaluate and respond to potential threats. The lateral septum (LS) is a structure in the ventral forebrain that calibrates the magnitude of behavioral responses to stress-related external stimuli, including the regulation of threat avoidance. The complex connectivity between the LS and other parts of the brain, together with its largely unexplored neuronal diversity, makes it difficult to understand how defined LS circuits control specific behaviors. Here, we describe a mouse model where the deletion of the transcriptional regulator Prdm16 in cells with a common developmental origin (Nkx2.1-lineage) results in the almost complete ablation of neurons from this lineage in the LS. Using a combination of single-nucleus RNA sequencing, histological and electrophysiological methods and behavioral analyses, we discovered that Crhr2-expresssing neurons are specifically affected in mutant mice, resulting in connectivity and electrophyisiological defects. This neuronal population is specifically activated in stressful contexts, and its removal results in increased exploratory behavior, even under stressful conditions. Our study extends the current knowledge about how defined neuronal populations within the LS can evaluate contextual information to select appropriate behavioral responses. This is a necessary step towards understanding the crucial role that the LS plays in neuropsychiatric conditions where defensive behavior is dysregulated, such as anxiety and aggression disorders.

neuroscience↗

bioRxiv2021

Transcriptional profiling of sequentially generated septal neuron fates

The septum is a ventral forebrain structure known to regulate innate behaviors. During embryonic development, septal neurons are produced in multiple proliferative areas from neural progenitors following transcriptional programs that are still largely unknown. Here, we use a combination of single cell RNA sequencing, histology and genetic models to address how septal neuron diversity is established during neurogenesis. We find that the transcriptional profiles of septal progenitors change along neurogenesis, coinciding with the generation of distinct neuron types. We characterize the septal eminence, a spatially distinct and transient proliferative zone composed of progenitors with distinctive molecular profiles, proliferative capacity and fate potential compared to the rostral septal progenitor zone. We show that Nkx2.1-expressing septal eminence progenitors give rise to neurons belonging to at least three morphological classes, born in temporal cohorts that are distributed across different septal nuclei in a sequential fountain-like pattern. Our study provides insight into the molecular programs that control the sequential production of different neuronal types in the septum, a structure with important roles in regulating mood and motivation.

neuroscience↗

bioRxiv2020

Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region specific manner

The cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine. However, the neurotransmitters released by cortical ChAT+ neurons and their synaptic connectivity are unknown. We show that the nearly all cortical ChAT+ neurons are specialized VIP+ interneurons that release GABA strongly onto other inhibitory interneurons and acetylcholine sparsely onto layer 1 interneurons and other VIP+/ChAT+ interneurons. This differential transmission of ACh and GABA based on the postsynaptic target neuron is reflected in VIP+/ChAT+ interneuron pre-synaptic terminals, as quantitative molecular analysis shows that only a subset of these are specialized to release acetylcholine. In addition, we identify a separate, sparse population of non-VIP ChAT+ neurons in the medial prefrontal cortex with a distinct developmental origin that robustly release acetylcholine in layer 1. These results demonstrate both cortex-region heterogeneity in cortical ChAT+ interneurons and target-specific co-release of acetylcholine and GABA.

neuroscience↗

bioRxiv2019

Transcriptional regulation of MGE progenitor proliferation by PRDM16 controls cortical GABAergic interneuron production

The mammalian cortex is populated by neurons derived from neural progenitors located throughout the embryonic telencephalon. Excitatory neurons are derived from progenitors located in the dorsal telencephalon, while inhibitory interneurons are generated by ventral telencephalic progenitors. The transcriptional regulator PRDM16 is expressed by radial glia, neural progenitors present in both regions; however, its mechanisms of action are still not fully understood. It is unclear if PRDM16 functions plays a role in neurogenesis in both dorsal and ventral progenitor lineages, and if so, whether it does so by regulating common or unique networks of genes. Here, we show that Prdm16 expression in MGE progenitors is required for maintaining their proliferative capacity and for the production of proper numbers of pallial GABAergic interneurons. PRDM16 binds to cis-regulatory elements and represses the expression of region-specific neuronal differentiation genes, thereby controlling the timing of neuronal maturation. Our results highlight the importance of PRDM16 for the development of both excitatory and inhibitory cortical circuits. We demonstrate the existence of convergent developmental gene expression programs regulated by PRDM16, which utilize both common and region-specific sets of genes in the cortex and the MGE to control the proliferative capacity of neural progenitors, ensuring the generation of correct numbers of cortical neurons.

neuroscience↗