bioRxiv Subject Collection: Neuroscience's Journal
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Monday, July 8th, 2024
| Time |
Event |
| 1:48p |
Valence and Salience Encoding in the Central Amygdala
The central amygdala (CeA) has emerged as an important brain region for regulating both negative (fear and anxiety) and positive (reward) affective behaviors. The CeA has been proposed to encode affective information in the form of valence (whether the stimulus is good or bad) or salience (how significant is the stimulus), but the extent to which these two types of stimulus representation occur in the CeA is not known. Here, we used single cell calcium imaging in mice during appetitive and aversive conditioning and found that majority of CeA neurons (~65%) encode the valence of the unconditioned stimulus (US) with a smaller subset of cells (~15%) encoding the salience of the US. Valence and salience encoding of the conditioned stimulus (CS) was also observed, albeit to a lesser extent. These findings show that the CeA is a site of convergence for encoding oppositely valenced US information. | | 1:48p |
Diffusion Basis Spectrum Imaging of White Matter in Schizophrenia and Bipolar Disorder
Background: Multiple studies point to the role of neuroinflammation in the pathophysiology of schizophrenia (SCZ), however, there have been few in vivo tools for imaging brain inflammation. Diffusion basis spectrum imaging (DBSI) is an advanced diffusion-based MRI method developed to quantitatively assess microstructural alternations relating to neuroinflammation, axonal fiber, and other white matter (WM) pathologies. Methods: We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n =27), schizophrenia (SCZ, n =21), and bipolar disorder (BPD, n =21) participants aged 18-30. We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain WM analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between groups. Clinical relationships of DBSI metrics with clinical symptoms were assessed across SCZ and control participants. Results: In SCZ participants, we found a generalized increase in DBSI-derived cellularity (a putative marker of neuroinflammation), a decrease in restricted fiber fraction (a putative marker of apparent axonal density), and an increase in extra-axonal water (a putative marker of vasogenic edema) across several WM tracts. There were only minimal WM abnormalities noted in BPD, mainly in regions of the corpus callosum (increase in DTI-derived RD and extra-axonal water). DBSI metrics showed significant partial correlations with psychosis and mood symptoms across groups. Conclusion: Our findings suggest that SCZ involves generalized white matter neuroinflammation, decreased fiber density, and demyelination, which is not seen in bipolar disorder. Larger studies are needed to identify medication-related effects. DBSI metrics could help identify high-risk groups requiring early interventions to prevent the onset of psychosis and improve outcomes. | | 1:48p |
Inhibitory neurons defined by a synaptogenic molecule impair memory discrimination
The CA3 region is central to hippocampal function during learning and memory because of its unique connectivity. CA3 pyramidal neurons are the targets of huge, excitatory mossy fiber synapses from DG axons and have an unusually high degree of excitatory recurrent connectivity. Thus, inhibition likely plays an outsized importance in constraining runaway excitation and shaping CA3 ensembles during learning and memory. Here, we investigate the function of a group of dendrite-targeting, hippocampal GABAergic neurons defined by expression of the synaptogenic adhesion molecule, Kirrel3. We discovered that activating Kirrel3-expressing GABAergic neurons impairs memory discrimination by inhibiting CA3 pyramidal neurons in novel contexts. Kirrel3 is required for DG-to-GABA synapse formation and variants in Kirrel3 are strong risk factors for neurodevelopmental disorders. Thus, our work suggests that Kirrel3-GABA neurons are a critical source of feed-forward inhibition from DG to CA3 during contextual memory whose activity may be specifically disrupted in some brain disorders. | | 1:48p |
Organizational principles of the primate cerebral cortex at the single-cell level
The primate cerebral cortex, the major organ for cognition, consists of an immense number of neurons. However, the organizational principles governing these neurons remain unclear. By accessing the single-cell spatial transcriptome of over 25 million neuron cells across the entire macaque cortex, we discovered that the distribution of neurons within cortical layers is highly non-random. Strikingly, over three-quarters of these neurons are located in distinct neuronal clusters. Within these clusters, different cell types tend to collaborate rather than function independently. Typically, excitatory neuron clusters mainly consist of excitatory-excitatory combinations, while inhibitory clusters primarily contain excitatory-inhibitory combinations. Both cluster types have roughly equal numbers of neurons in each layer. Importantly, most excitatory and inhibitory neuron clusters form spatial partnerships, indicating a balanced local neuronal network and correlating with specific functional regions. These findings suggest that different brain regions of the primate cortex may exhibit similar mechanisms at the neuronal population level. |
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