Types Of Neurons Research Articles

Adverse Reactions to the Orphan Drug Cerliponase Alfa in the Treatment of Neurolipofuscinosis Type 2 (CLN2)

Background/Objectives: Neuronal Ceroid Lipofuscinosis type 2 is a rare pathology affecting mainly the central nervous system (CNS) and retina, and is caused by variants in the gene encoding the lysosomal enzyme tripeptidyl peptidase 1. Therapy with enzyme replacement through the brain infusion of the orphan drug cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme replacement therapy delivered via intracerebroventricular infusion, has been approved for Neuronal Ceroid Lipofuscinosis type 2 disease. The safety profile of cerliponase alfa has been established based on pre-authorization studies; currently, no post-marketing investigation has been performed to confirm it. Here, a descriptive analysis of real-world spontaneous reporting data of suspected adverse reactions (SARs) to cerliponase alfa in the EudraVigilance database was performed to compile clear information on the safety profile. Methods: Suspected adverse reactions to cerliponase alfa reported in the data system EudraVigilance were analyzed for age, sex of the patient, adverse reactions, and the indication for use. Results: Cases with suspected adverse reactions to cerliponase alfa were found to be more frequent in female patients (58.1%) and in children aged 3–11 years. The most common adverse reactions were, in decreasing order, fever/pyrexia, device-related infection, vomiting, seizures/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. Conclusions: The results confirm the safety profile of cerliponase alfa established with pre-registration clinical studies but suggest the need for further studies to investigate the occurrence of adverse reactions, as possible predictive prognostic markers, in more depth.

TMIC-18. ROLE OF NEUROTRANSMITTERS IN GLIOBLASTOMA PATHOPHYSIOLOGY: EMERGING INSIGHTS

Abstract INTRODUCTION Glioblastoma (GBM) are the most common primary brain tumor in adults associated with a dismal patient outcome. While it is well-known that glutamatergic neurons can form functional synapses with glioblastoma cells to enhance tumor growth, lesser is known about the effects of activity of other neuronal types on glioblastoma biology, especially among different glioblastoma molecular subtypes. Here, we examined the effects of various neurotransmitters on the growth of glioblastoma cells characterized as classical, proneural and mesenchymal subtypes. METHODS Patient-derived glioblastoma cell lines were exposed to varying concentrations of different neurotransmitters and assessed for cell viability using CCK-8 assay. Transcriptomic data from TCGA (The Cancer Genome Atlas) database was analyzed for correlation of expression of neurotransmitter receptors (NTRs) with patient survival. Using IVY-GAP database, we compared the expression of NTRs at leading-edge versus tumor core of tumors to assess their possible involvement in cell migration and microenvironmental interactions. RESULTS Consistent with previous findings, we observed an increase in cell viability in all GBM cell lines after being incubated with L-glutamate. The classical subtype has a stronger growth response to L-glutamate compared to the other two subtypes. TCGA data revealed the expression of GRIK4 (glutamate ionotropic receptor kainate type subunit 4) as highest in the classical subtype as well as inversely correlated with worse patient survival in this GBM subtype, as opposed to proneural or mesenchymal patient groups. CCK8 assay also suggested that acetylcholine and dopamine increase glioblastoma cell growth. A subset of cholinergic and glutamatergic receptors (CHRM1, GRM2) was found upregulated in infiltrating/leading-edge regions of glioblastoma tumors compared to the tumor core, suggesting possible involvement in glioblastoma-neuron interactions. CONCLUSION Our findings suggest that GBM subtypes may differentially leverage neuro-modulatory mechanisms to support their growth. Future studies will investigate the differential neuronal responses in GBM subtypes using pharmacological/genetic approaches.

Targeted deletion of olfactory receptors in D. melanogaster via CRISPR/Cas9-mediated LexA knock-in

The study of olfaction in Drosophila melanogaster has greatly benefited from genetic reagents such as olfactory receptor mutant lines and GAL4 reporter lines. The CRISPR/Cas9 gene-editing system has been increasingly used to create null receptor mutants or replace coding regions with GAL4 reporters. To further expand this toolkit for manipulating fly olfactory receptor neurons (ORNs), we generated null alleles for 11 different olfactory receptors by using CRISPR/Cas9 to knock in LexA drivers, including multiple lines for receptors which have thus far lacked knock-in mutants. The targeted neuronal types represent a broad range of antennal ORNs from all four morphological sensillum classes. Additionally, we confirmed their loss-of-function phenotypes, assessed receptor haploinsufficiency, and evaluated the specificity of the LexA knock-in drivers. These receptor mutant lines have been deposited at the Bloomington Drosophila Stock Center for use by the broader scientific community.

Therapeutic effects of pentoxifylline in propionic acid‐induced autism symptoms in rat models: A behavioral, biochemical, and histopathological study

AbstractObjectiveThe role of propionic acid (PPA) in eliciting behaviors analogous to autism in rat models is a documented phenomenon. This study examines the therapeutic implications of pentoxifylline—an agent traditionally used for peripheral vascular diseases—on these autism‐like behaviors by modulating brain proteins and reducing pro‐inflammatory cytokines like tumor necrosis factor‐α (TNF‐α) in a rat model.MethodsThis research involved 30 male Wistar albino rats, which were divided into three distinct groups: a baseline control set, a PPA‐treated cluster receiving a 250 mg/kg/day dose of PPA via intraperitoneal injection for a span of five days followed by saline orally, and a PPA group administered an oral dose of pentoxifylline at 300 mg/kg/day over 15 days. Subsequent to the treatment phase, euthanasia was carried out for the extraction of brain and blood samples, which were then analyzed for histopathological and biochemical markers.ResultsThe pentoxifylline‐treated subjects demonstrated a significant mitigation in the manifestation of autistic‐like behaviors, as assessed through a triad of social interaction tests. A noteworthy decline in TNF‐α levels was observed, alongside a significant rise in the concentration of adenosine triphosphate and nerve growth factor in brain tissue (p < 0.05). Histopathological analysis underscored a reduction in oxidative stress and a significant preservation of neuronal cell types, specifically pyramidal neurons in the hippocampal CA1 and CA3 regions and Purkinje cells in the cerebellum (p < 0.001).ConclusionPentoxifylline treatment has been found to effectively reduce the behavioral symptoms associated with autism, as well as biochemical and histopathological disruptions induced by PPA in rat models, highlighting its potential as a neurotherapeutic agent.

Distinct inhibitory neurons differently shape neuronal codes for sound intensity in the auditory cortex

Cortical circuits contain multiple types of inhibitory neurons which shape how information is processed within neuronal networks. Here, we asked whether somatostatin-expressing (SST) and vasoactive intestinal peptide-expressing (VIP) inhibitory neurons have distinct effects on population neuronal responses to noise bursts of varying intensities. We optogenetically stimulated SST or VIP neurons while simultaneously measuring the calcium responses of populations of hundreds of neurons in the auditory cortex of male and female awake, head-fixed mice to sounds. Upon SST neuronal activation, noise bursts representations became more discrete for different intensity levels, relying on cell identity rather than strength. By contrast, upon VIP neuronal activation, noise bursts of different intensity level activated overlapping neuronal populations, albeit at different response strengths. At the single-cell level, SST and VIP neuronal activation differentially modulated the response-level curves of monotonic and nonmonotonic neurons. SST neuronal activation effects were consistent with a shift of the neuronal population responses toward a more localist code with different cells responding to sounds of different intensity. By contrast, VIP neuronal activation shifted responses towards a more distributed code, in which sounds of different intensity level are encoded in the relative response of similar populations of cells. These results delineate how distinct inhibitory neurons in the auditory cortex dynamically control cortical population codes. Different inhibitory neuronal populations may be recruited under different behavioral demands, depending on whether categorical or invariant representations are advantageous for the task.Significance StatementInformation about sounds is represented in the auditory cortex by neuronal population activity that has a characteristic sparse structure. Cortical neuronal populations comprise multiple types of excitatory and inhibitory neurons. Here, we find that activating different types of inhibitory neurons differentially controls population neuronal representations, with one type of inhibitory neurons increasing the differences in the identity of the cells recruited to represent the different sounds, and another inhibitory neuron type changing the relative activity level of overlapping neuronal populations. Such transformations may be beneficial for different types of auditory behaviors, suggesting that these different types of inhibitory neurons may be recruited under different behavioral constraints in optimizing neuronal representations of sounds.

The brain atlas of a subsocial bee reflects that of eusocial Hymenoptera.

The evolutionary transition from solitary life to group-living in a society with cooperative brood care, reproductive division of labor and morphological castes is associated with increased cognitive demands for task-specialization. Associated with these demands, the brains of eusocial Hymenoptera divide transcriptomic signatures associated with foraging and reproduction to different populations of cells and also show diverse astrocyte and Kenyon cell types compared with solitary non-hymenopteran insects. The neural architecture of subsocial bees, which represent evolutionary antecedent states to eusocial Hymenoptera, could then show how widely this eusocial brain is conserved across aculeate Hymenoptera. Using single-nucleus transcriptomics, we have created an atlas of neuron and glial cell types from the brain of a subsocial insect, the small carpenter bee (Ceratina calcarata). The proportion of C. calcarata neurons related to the metabolism of classes of neurotransmitters is similar to that of other insects, whereas astrocyte and Kenyon cell types show highly similar gene expression patterns to those of eusocial Hymenoptera. In the winter, the transcriptomic signature across the brain reflected diapause. When the bee was active in the summer, however, genes upregulated in neurons reflected foraging, while the gene expression signature of glia associated with reproductive functions. Like eusocial Hymenoptera, we conclude that neural components for foraging and reproduction in C. calcarata are compartmentalized to different parts of its brain. Cellular examination of the brains of other solitary and subsocial insects can show the extent of neurobiological conservation across levels of social complexity.

Neuronal fate resulting from indirect neurogenesis in the mouse neocortex

Abstract Excitatory cortical neurons originate from cortical radial glial cells (RGCs). Initially, these neurons were thought to derive directly from RGCs (direct neurogenesis) and be distributed in an inside-out fashion. However, the discovery of indirect neurogenesis, whereby intermediate neuronal progenitors (INPs) generate neurons, challenged this view. To investigate the integration of neurons via these two modes, we developed a method to identify INP progeny and analyze their fate using transgenic mice expressing tamoxifen-inducible Cre recombinase under the neurogenin-2 promoter, alongside thymidine analog incorporation. Their fate was further analyzed using mosaic analysis with double markers in mice. Indirect neurogenesis was prominent during early neurogenesis, generating neuron types that would emerge slightly later than those produced via direct neurogenesis. Despite the timing difference, both neurogenic modes produced fundamentally similar neuron types, as evidenced by marker expression and cortical-depth location. Furthermore, INPs generated pairs of similar phenotype neurons. These findings suggest that indirect neurogenesis, like direct neurogenesis, generates neuron types in a temporally ordered sequence and increases the number of similar neuron types, particularly in deep layers. Thus, both neurogenic modes cooperatively generate a diverse array of neuron types in a similar order, and their progeny populate together to form a coherent cortical structure.

Leveraging deep single-soma RNA sequencing to explore the neural basis of human somatosensation.

The versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons. However, soma transcriptomes of individual human (h)DRG neurons-critical information to decipher their functions-are lacking due to technical difficulties. In this study, we isolated somata from individual hDRG neurons and conducted deep RNA sequencing (RNA-seq) to detect, on average, over 9,000 unique genes per neuron, and we identified 16 neuronal types. These results were corroborated and validated by spatial transcriptomics and RNAscope in situ hybridization. Cross-species analyses revealed divergence among potential pain-sensing neurons and the likely existence of human-specific neuronal types. Molecular-profile-informed microneurography recordings revealed temperature-sensing properties across human sensory afferent types. In summary, by employing single-soma deep RNA-seq and spatial transcriptomics, we generated an hDRG neuron atlas, which provides insights into human somatosensory physiology and serves as a foundation for translational work.

Molecular Lineages and Spatial Distributions of Subplate Neurons in the Human Fetal Cerebral Cortex.

The expansion of neural progenitors and production of distinct neurons are crucial for architectural assembly and formation of connectivity in human brains. Subplate neurons (SPNs) are among the firstborn neurons in the human fetal cerebral cortex, and play a critical role in establishing intra- and extracortical connections. However, little is known about SPN origin and developmental lineages. In this study, spatial landscapes and molecular trajectories of SPNs in the human fetal cortices from gestational weeks (GW) 10 to 25 are created by performing spatial transcriptomics and single-cell RNA sequencing. Genes known to be evolutionarily human-specific and genes associated with extracellular matrices (ECMs) are found to maintain stable proportions of subplate neurons among other neuronal types. Enriched ECM gene expression in SPNs varies in distinct cortical regions, with the highest level in the frontal lobe of human fetal brains. This study reveals molecular origin and lineage specification of subplate neurons in the human fetal cerebral cortices, and highlights underpinnings of SPNs to cortical neurogenesis and early structural folding.

Activation of 5-HT7 receptors in the mouse dentate gyrus does not affect theta-burst-induced plasticity at the perforant path synapse.

The study examined the effects of 5-HT7 receptor activation on GABAergic transmission within the dentate gyrus and plasticity at the glutamatergic perforant path input. Immunofluorescence imaging was performed using transverse hippocampal slices from transgenic mice expressing green fluorescent protein (GFP) under the Htr7 promoter. This was followed by whole-cell patch clamp electrophysiological recordings assessing the effects of pharmacologically activating 5-HT7 receptors on spontaneous inhibitory postsynaptic currents recorded from dentate granule cells and hilar mossy cells-two glutamatergic neuron types present in the dentate gyrus. Extracellular recordings of field excitatory postsynaptic potentials were then performed to assess whether 5-HT7 receptor activation influenced theta-burst stimulation-evoked plasticity of the perforant path synaptic input. It was found that parvalbumin and somatostatin interneurons in the dentate gyrus expressed GFP, which suggests they express 5-HT7 receptors. However, activation of 5-HT7 receptors had no effect on GABAergic transmission targeting mossy cells or granule cells. There was also no effect of 5-HT7 receptor activation on perforant path plasticity either with intact or blocked GABAA receptor signaling. The presence of 5-HT7 receptors in a subset of parvalbumin and somatostatin interneurons in the mouse dentate gyrus could mean that they are involved in the inhibitory control of dentate gyrus activity. However, this potential effect was not evident in slice recordings of inhibitory transmission targeting principal cells and did not affect perforant path plasticity. Further experiments are needed to fully elucidate the functional role of these receptors in the dentate gyrus.

Ablation of NAMPT in dopaminergic neurons leads to neurodegeneration and induces Parkinson’s disease in mouse

Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in the salvaging synthesize pathway of nicotinamide adenine dinucleotide (NAD). The neuroprotective roles of NAMPT on neurodegeneration have been explored in aging brain and Alzheimer’s Disease. However, its roles in Parkinson’s Disease (PD) remain to be elucidated. We found that the dopaminergic neurons in substantia nigra expressed higher levels of NAMPT than the other types of neurons. Using conditional knockout of the Nampt gene in dopaminergic neurons and utilizing a NAMPT inhibitor in the substantia nigra of mice, we found that the NAMPT deficiency triggered the time-dependent loss of dopaminergic neurons, the impairment of the dopamine nigrostriatal pathway, and the development of PD-like motor dysfunction. In the rotenone-induced PD mouse model, nicotinamide ribose (NR), a precursor of NAD, rescued the loss of dopaminergic neurons, the impairment of dopamine nigrostriatal pathway, and mitigated PD-like motor dysfunction. In SH-SY5Y cells, NAD suppression induced the accumulation of reactive oxygen species (ROS), mitochondrial impairment, and cell death, which was reversed by N-acetyl cysteine, an antioxidant and ROS scavenger. Rotenone decreased NAD level, induced the accumulation of ROS and the impairment of mitochondria, which was reversed by NR. In summary, our findings show that the ablation of NAMPT in dopaminergic neurons leads to neurodegeneration and contributes to the development of PD. The NAD precursors have the potential to protect the degeneration of dopaminergic neurons, and offering a therapeutic approach for the treatment of PD.

Complex Brain Morphology Discovered in the Shark Parasite Nybelinia surmenicola (Cestoda: Trypanorhyncha).

The ultrastructure of the nervous system has been studied in sexually mature Nybelinia surmenicola (Cestoda: Trypanorhyncha) from the intestine of a shark Lamna ditropis. The central nervous system (CNS) reveals a complex organization within cestodes and corresponds to the trypanorhynch pattern of brain architecture. The brain of N. surmenicola is differentiated into nine clearly defined lobes and semicircular, median, and X-shaped cruciate commissures. A specific feature is the presence of a powerful extracellular capsule that surrounds the brain lobes with the cortical glial cells. Moreover, the architecture of the anterior lobes clearly distinguishes the species of Tentacularioidea. The neurons of the anterior lobes form compact groups looking like frontal horns. There are approximately 120 neurons in the anterior lobes and a preliminary estimate of more than 300 perikarya in the brain. Several ultrastructural types of neurons have been identified, differing in the size and shape of the soma, the density of the cytoplasm, and the ultrastructure of synaptic vesicles. Numerous synapses involving clear and electron-dense vesicles have been observed in neuropils. Two types of glial cells have been found in the brain that participate in neuronal metabolism and wrap around the giant axons, brain lobes, neuropil compartments, and the main nerve cords. Such a powerful extracellular fibrillar brain capsule has not been observed in the brain of other studied cestodes and has been demonstrated in this study for the first time. The differentiation of the brain lobes reveals the important role of the rhyncheal system in the evolution of cestodes and correlates with their behavior. The anterior nerves arising from the anterior lobes innervate the radial muscles stabilizing the position of the tentacle sheaths and movements of the attachment organs. The nervous system anatomy and the brain architecture may reflect the morphofunctional aspects of the tapeworm evolution.

Repercussion of Primary Nucleation Pathway: Dementia and Cognitive Impairment.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and prion disease, are characterized by the conversion of normally soluble proteins or peptides into aggregated amyloidal fibrils. These diseases result in the permanent loss of specific types of neurons, making them incurable and devastating. Research on animal models of memory problems mentioned in this article contributes to our knowledge of brain health and functionality. Neurodegenerative disorders, which often lead to cognitive impairment and dementia, are becoming more prevalent as global life expectancy increases. These diseases cause severe neurological impairment and neuronal death, making them highly debilitating. Exploring and understanding these complex diseases offer significant insights into the fundamental processes essential for maintaining brain health. Exploring the intricate mechanisms underlying neurodegenerative diseases not only holds promise for potential treatments but also enhances our understanding of fundamental brain health and functionality. By unraveling the complexities of these disorders, researchers can pave the way for advancements in diagnosis, treatment, and ultimately, improving the lives of individuals affected by neurodegenerative diseases.

Cortico-thalamic communication for action coordination in a skilled motor sequence.

The coordination of forelimb and orofacial movements to compose an ethological reach-to-consume behavior likely involves neural communication across brain regions. Leveraging wide-field imaging and photo-inhibition to survey across the cortex, we identified a cortical network and a high-order motor area (MOs-c), which coordinate action progression in a mouse reach-and-withdraw-to-drink (RWD) behavior. Electrophysiology and photo-inhibition across multiple projection neuron types within the MOs-c revealed differential contributions of pyramidal tract and corticothalamic (CT MOs ) output channels to action progression and hand-mouth coordination. Notably, CT MOs display sustained firing throughout RWD sequence and selectively enhance RWD-relevant activity in postsynaptic thalamus neurons, which also contribute to action coordination. CT MOs receive converging monosynaptic inputs from forelimb and orofacial sensorimotor areas and are reciprocally connected to thalamic neurons, which project back to the cortical network. Therefore, motor cortex corticothalamic channel may selectively amplify the thalamic integration of cortical and subcortical sensorimotor streams to coordinate a skilled motor sequence.

Distinct Neuron Types Contribute to Hybrid Auditory Spatial Coding.

Neural decoding is a tool for understanding how activities from a population of neurons inside the brain relate to the outside world and for engineering applications such as brain-machine interfaces. However, neural decoding studies mainly focused on different decoding algorithms rather than different neuron types which could use different coding strategies. In this study, we used two-photon calcium imaging to assess three auditory spatial decoders (space map, opponent channel, and population pattern) in excitatory and inhibitory neurons in the dorsal inferior colliculus of male and female mice. Our findings revealed a clustering of excitatory neurons that prefer similar interaural level difference (ILD), the primary spatial cues in mice, while inhibitory neurons showed random local ILD organization. We found that inhibitory neurons displayed lower decoding variability under the opponent channel decoder, while excitatory neurons achieved higher decoding accuracy under the space map and population pattern decoders. Further analysis revealed that the inhibitory neurons' preference for ILD off the midline and the excitatory neurons' heterogeneous ILD tuning account for their decoding differences. Additionally, we discovered a sharper ILD tuning in the inhibitory neurons. Our computational model, linking this to increased presynaptic inhibitory inputs, was corroborated using monaural and binaural stimuli. Overall, this study provides experimental and computational insight into how excitatory and inhibitory neurons uniquely contribute to the coding of sound locations.

Photoinduced Online Enrichment-Deglycosylation of Glycolipids for Enhancing Lipid Coverage and Identification in Single-Cell Mass Spectrometry.

Single-cell lipidomics provides important information for molecular mechanisms of living processes and diseases at the individual cell level. However, single-cell lipidomic mass spectrometry (MS) techniques suffer from low lipid coverage and incomplete structural elucidation, especially for poorly ionizable glycosphingolipids (GSLs). Herein, a photoinduced enrichment-deglycosylation method of GSLs was developed and introduced into an ambient liquid extraction MS system for enhancing detection coverage and identification accuracy of GSLs in single-cell MS. GSL standards were selectively adsorbed on TiO2 in ammonia-added protic solvents. Under UV irradiation, the adsorbed GSLs would lose one hexosyl group (deglycosylation), and the products (>70% conversion efficiency) were desorbed from TiO2. By coating porous TiO2 into the capillary of the ambient liquid extraction MS system, online adsorption of GSLs and their separation from high-abundance phospholipids were achieved, largely reducing ion suppression. By UV irradiation, captured GSLs were rapidly deglycosylated and photodesorbed from TiO2 coating without solvent switching, resulting in 6-fold enrichment. With the new method, the detection coverage of GSLs was enhanced 9-fold without losing other lipidomes, compared with the conventional method. Moreover, deglycosylated GSLs from photodesorption had more MS/MS fragments than intact GSLs, facilitating detailed fatty acyl and sphingosine chain elucidation. Seven deglycosylated GSL peaks were identified with the confirmed hydroxyl group location in the fatty acyl chain, while only 1 was identified for intact GSL. The new method was applied to the single-cell lipidomics study of two types of nerve cells. Totally, 31 lipids including 11 GSLs were identified in a single cell, and 5 hexosylceramides were found significantly altered after neuron injury.

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit.

In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.

Thalamus of Reptiles and Mammals: Some Significant Differences.

Most studies comparing forebrain organization between reptiles and mammals have focused on similarities. Equally important are the differences between their brains. While differences have been addressed infrequently, this approach can highlight the evolution of brains in relation to their respective environments. This review focuses on three key differences between the dorsal and ventral thalamus of reptiles and mammals. One is the organization of thalamo-telencephalic interconnections. Reptiles have at least three circuits that transmit information between the dorsal thalamus and telencephalon whereas mammals have just one. A second is the number and distribution of local circuit neurons in the dorsal thalamus. Most reptilian dorsal thalamic nuclei lack local circuit neurons whereas these same nuclei in mammals contain varying numbers. The third is the organization of the thalamic reticular nucleus. In crocodiles, at least, the neurons in the thalamic reticular nucleus are heterogeneous with two separate nuclei each being associated with a different circuit. In mammals, the neurons in the thalamic reticular nucleus, which is a single structure, are homogeneous. Transcriptomics and development are suggested to be the most likely approaches to explain these differences between reptiles and mammals. Transcriptomics can reveal which neuron types are 'new' or 'old' and whether neurons and their respective circuits have been re-purposed to be used differently. Examination of the development and connections of the dorsal and ventral thalamus will determine whether their formation is similar or different from what has been described for mammals.

Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates.

The amygdaloid complex mediates learning, memory, and emotions. Understanding the cellular and anatomical features that are specialized in the amygdala of primates versus other vertebrates requires a systematic, anatomically-resolved molecular analysis of constituent cell populations. We analyzed five nuclear subdivisions of the primate amygdala with single-nucleus RNA sequencing in macaques, baboons, and humans to examine gene expression profiles for excitatory and inhibitory neurons and confirmed our results with single-molecule FISH analysis. We identified distinct subtypes of FOXP2 + interneurons in the intercalated cell masses and protein-kinase C-δ interneurons in the central nucleus. We also establish that glutamatergic, pyramidal-like neurons are transcriptionally specialized within the basal, lateral, or accessory basal nuclei. Understanding the molecular heterogeneity of anatomically-resolved amygdalar neuron types provides a cellular framework for improving existing models of how amygdalar neural circuits contribute to cognition and mental health in humans by using nonhuman primates as a translational bridge.

Compressed sensing based approach identifies modular neural circuitry driving learned pathogen avoidance.

An animal's survival hinges on its ability to integrate past information to modify future behavior. The nematode C. elegans adapts its behavior based on prior experiences with pathogen exposure, transitioning from attraction to avoidance of the pathogen. A systematic screen for the neural circuits that integrate the information of previous pathogen exposure to modify behavior has not been feasible because of the lack of tools for neuron type specific perturbations. We overcame this challenge using methods based on compressed sensing to efficiently determine the roles of individual neuron types in learned avoidance behavior. Our screen revealed that distinct sets of neurons drive exit from lawns of pathogenic bacteria and prevent lawn re-entry. Using calcium imaging of freely behaving animals and optogenetic perturbations, we determined the neural dynamics that regulate one key behavioral transition after infection: stalled re-entry into bacterial lawns. We find that key neuron types govern pathogen lawn specific stalling but allow the animal to enter nonpathogenic E. coli lawns. Our study shows that learned pathogen avoidance requires coordinated transitions in discrete neural circuits and reveals the modular structure of this complex adaptive behavioral response to infection.