Biology subjects

Navarro, V. I.

Publications and source records attributed to Navarro, V. I..

4 recordsLinked to original sources

bioRxiv2025

Elaborating the connections of a closed-loop forebrain circuit in the rat: Circumscribed evidence for novel topography within a cortico-striato-pallidal triple descending projection, with thalamic feedback, to the anterior lateral hypothalamic area

Motivated behaviors are regulated by distributed forebrain networks. Traditional approaches have often focused on individual brain regions and connections that do not capture the topographic organization of forebrain connectivity. We performed co-injections of anterograde and retrograde tract tracers in rats to provide novel high-spatial resolution evidence of topographic connections that elaborate a previously identified closed-loop forebrain circuit implicated in affective and motivational processes. The nodes of this circuit include select regions of the medial prefrontal cortex (defined here more specifically as the cingulate region, CNG), a dorsomedial portion of the nucleus accumbens (ACBdm), a portion of the medial substantia innominata (SIm), and the anterior lateral hypothalamic area (LHAa). The circuit also reportedly receives a feedback loop from the anterior region of the paraventricular thalamic nucleus (PVTa). In this draft report, we provide detailed circumscribed evidence supporting these regions as interconnected nodes, and provide several novel findings concerning the topographic organization of their projections. First, we identified the ACBdm based on its unique connectivity. Anterograde labeling from anterior paraventricular thalamic nucleus (PVTa) and retrograde labeling from medial substantia innominata (SIm) and lateral hypothalamic area (LHA) were restricted to the dorsomedial ACB (ACBdm). Strikingly, this labeling formed a longitudinal column extending along virtually the entire anteroposterior axis of ACBdm. Subsequent analysis revealed a convergence of ACBdm axon terminals and retrogradely labeled neurons from LHA within the anterior SIm. Furthermore, we identified cortical CNG regions related to this circuit. These regions contained retrograde labeling from both ACBdm and LHA, and anterograde labeling from PVTa. These cortical subdomains included regions previously implicated in the circuit but for which detailed organization has been unknown: (1) a region between the posterior prelimbic and infralimbic areas; (2) posterior part of basolateral and basomedial amygdalar nuclei, and (3) anterior pole of ventral subiculum. Our circumscribed findings, which await additional samples and analysis, support the existence of a topographically organized closed-loop circuit and identify two additional novel features: (1) direct evidence for an elaborate core rostrocaudal topography for a cortico-striato-pallidal motif comprising a triple descending projection to the LHA via direct, indirect, and "hyperdirect" pathways, and (2) a thalamic feedback system with specific projections to each cortical and striatal node of the circuit. We discuss the implications of this newly elaborated circuit for understanding the neural basis of motivational processes. Significance StatementWe used a bottom-up approach to identify a distinct longitudinal column of dorsomedial nucleus accumbens (ACBdm) that spans its anteroposterior axis. This region projects to medial substantia innominata (SIm) and lateral hypothalamic area (LHA), resembling the "direct" and "indirect" pathways of the classical basal ganglia circuit. We also identified topographically distinct regions in medial prefrontal cortex (strictly delineated here as the cingulate region, CNG), ventral subiculum (SUBv), and basolateral amygdala (BLA) that project to both ACBdm and LHA, further defining the circuit. Finally, we identified an LHA-to-anterior paraventricular thalamic nucleus (PVTa) feedback projection that selectively targets cortical and striatal nodes within the circuit. Our work provides novel detailed maps that bolster the proposal that this "triple descending projection" (cortico-striato-pallidal) and associated thalamic feedback loop play a role in affective and motivational processes.

neuroscience↗

bioRxiv2024

Chemoarchitectural studies of the rat hypothalamus and zona incerta.Chemopleth 1.0, a downloadable interactive Brain Maps spatial database of five co-visualizable neurochemical systems, with novel feature- and grid-based mapping tools

The hypothalamus and zona incerta of the brown rat (Rattus norvegicus), a model organism important for translational neuroscience research, contain diverse neuronal populations essential for survival, but how these populations are structurally organized as systems remains elusive. With the advent of novel gene-editing technologies and artificial intelligence, there is an apparent research need for high-spatial-resolution maps of rat hypothalamic neurochemical cell types to aid in their gene-directed targeting, to validate their expression in transgenic lines, or to supply precious ground-truth training data for machine learning algorithms. Here, we present Chemopleth 1.0 [available at: https://doi.org/10.5281/zenodo.15788189], a chemoarchitecture database for the rat hypothalamus (HY) and zona incerta (ZI), which features downloadable interactive maps featuring the census distributions of five immunoreactive neurochemical systems: (1) vasopressin (as detected from its gene co-product, copeptin); (2) neuronal nitric oxide synthase (EC 1.14.13.39); (3) hypocretin 1/orexin A; (4) melanin-concentrating hormone; and (5) alpha-melanocyte-stimulating hormone. These maps are formatted for the widely used Brain Maps 4.0 (BM4.0) open-access rat brain atlas (RRID:SCR_017314). Importantly, this dataset retains atlas stereotaxic coordinates that facilitate the precise targeting of the cell bodies and/or axonal fibers of these neurochemical systems, thereby potentially serving to streamline delivery of viral vectors for gene-directed manipulations. The maps are presented together with novel open-access tools to visualize the data, including a new workflow to quantify cell positions and fiber densities for BM4.0. The workflow produces "heat maps" of neurochemical distributions from multiple subjects: 1) isopleth maps that represent consensus distributions independent of underlying atlas boundary conditions, and 2) choropleth maps that provide distribution differences based on cytoarchitectonic boundaries. The database files, generated using the Adobe(R) Illustrator(R) vector graphics environment, can also be opened using the free vector graphics editor, Inkscape. We also introduce a refined grid-based coordinate system for this dataset, register it with previously published spatial data for the HY and ZI, and introduce novel grid-based annotation of experimental observations. This database provides critical spatial targeting information for these neurochemical systems unavailable from mRNA-based maps and allows readers to place their own datasets in register with them. It also provides a space for the continued buildout of a community-driven atlas-based spatial model of rat hypothalamic chemoarchitecture, allowing experimental observations from multiple laboratories to be registered to a common spatial framework.

neuroscience↗

bioRxiv2024

Topographic organization of bidirectional connections between the cingulate region (infralimbic area and anterior cingulate area, dorsal part) and the interbrain (diencephalon) of the adult male rat

The medial prefrontal cortex [cingulate region (Brodmann, 1909) (CNG)] in the rat is a connectionally and functionally diverse structure. It harbors cerebral nuclei that use long-range connections to promote adaptive changes to ongoing behaviors. The CNG is often described across functional and anatomical gradients, a dorsal-ventral gradient being the most prominent. Topographic organization is a general feature of the nervous system, and it is becoming clear that such spatial arrangements can reflect connectional, functional, and cellular differences. Portions of the CNG are known to form reciprocal connections with cortical areas and thalamus; however, these connectional features have not been described in detail or mapped to standardized rat brain atlases. Here, we used co-injected anterograde (Phaseolus vulgaris leucoagglutinin) and retrograde (cholera toxin B subunit) tracers throughout the CNG to identify zones of reciprocal connectivity in the diencephalon [or interbrain (Baer, 1837) (IB)]. Tracer distributions were observed using a Nissl-based atlas-mapping approach that facilitates description of topographic organization. This draft report describes CNG connections of the infralimbic area (Rose & Woolsey, 1948) (ILA) and the anterior cingulate area, dorsal part (Krettek & Price, 1977) (ACAd) throughout the IB. We found that corticothalamic connections are predominantly reciprocal, and that ILA and ACAd connections tended to be spatially segregated with minimal overlap. In the hypothalamus (Kuhlenbeck, 1927), we found dense and specific ILA-originating terminals in the following Brain Maps 4.0 atlas territories: dorsal region (Swanson, 2004) (LHAd) and suprafornical region (Swanson, 2004) (LHAs) of the lateral hypothalamic area (Nissl, 1913), parasubthalamic nucleus (Wang & Zhang, 1995) (PSTN), tuberal nucleus, terete part (Petrovich et al., 2001) (TUte), and an ill-defined dorsal cap of the medial mammillary nucleus (Gudden, 1881) (MM). We discuss these findings in the context of feeding behaviors.

neuroscience↗

bioRxiv2022

Glycemic challenge is associated with the rapid cellular activation of the locus ceruleus and nucleus of solitary tract: Circumscribed spatial analysis of phosphorylated MAP kinase immunoreactivity in relation to catecholaminergic and cholinergic chemoarchitecture

Rodent studies indicate that impaired glucose utilization or hypoglycemia is associated with cellular activation of neurons in the medulla (Winslow, 1733) (MY) believed to control feeding behavior and glucose counterregulation. However, such activation has been tracked primarily within hours of the challenge, rather than sooner, and has been poorly mapped within standardized brain atlases. Here, we report that within 15 min of receiving 2-deoxy-D-glucose (2-DG; 250 mg/kg, i.v.), which can trigger glucoprivic feeding behavior, marked elevations were observed in the numbers of rhombic brain (His, 1893) (RB) neuronal cell profiles immunoreactive for the cellular activation marker(s), phosphorylated p44/42 MAP kinases (phospho-ERK1/2), some of which were also catecholaminergic. We mapped their distributions within an open-access rat brain atlas and found that 2-DG-treated rats (compared to their saline-treated controls) displayed greater numbers of phospho-ERK1/2+ neurons in the locus ceruleus (Wenzel & Wenzel, 1812) (LC) and the nucleus of solitary tract (>1840) (NTS). Thus, 2-DG-activation of certain RB neurons is more rapid than perhaps previously realized, engaging neurons that serve multiple functional systems and are of varying cellular phenotypes. Mapping these populations within standardized brain atlas maps streamlines their targeting and/or comparable mapping in preclinical rodent models of disease.

neuroscience↗