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Hultman, I.

Publications and source records attributed to Hultman, I..

4 recordsLinked to original sources

Coordinated Brain-Network Dynamics of Maternal Adaptation

The maternal brain exhibits impressive plasticity, undergoing many anatomical and functional alterations over the transition to parenting. Such alterations can reflect maternal adaptation to offspring needs, aligning with the onset and maintenance of maternal care behaviors. These brain-wide neural changes occur across stages, starting during pregnancy and continuing through the peripartal transition. We therefore wanted to understand brain changes with pregnancy, parenting, and care behaviors over time. Many brain regions have been implicated in the coordination of maternal adaptation and corresponding care behaviors. We used computational modeling of multi-region neural oscillation data to identify distinct electrical networks during naturally-occurring care behaviors and across multiple maternal stages in outbred, highly maternal mice. This work demonstrates that multi-region oscillatory electrical dynamics at high spatiotemporal resolution reflect these functions. Distinct, discriminative networks predict maternal behavior and stage, showcasing network adaptation with parental transition. Maternal behavior and stage also had substantial effects on other distinct, multi-region oscillatory electrical networks relevant to stress susceptibility, further linking maternal adaptation to the neurophysiology of stress. While these stress networks were perturbed by maternal experience of early life stress, networks trained on maternal behavior and stage remained robust against such perturbation. This suggests a uniquely persistent strength of maternal electrical dynamics. Together, this work supports the role of oscillatory electrical dynamics as networks underlying fundamentally conserved behaviors and transitions, demonstrating wide relevance and significance to brain-behavior discovery.

neuroscience↗

Peripheral CGRP engages brain-wide electrical network activity of migraine

BackgroundMigraine is a disorder of severe, recurrent headaches and debilitating sensory, cognitive and affective symptoms, often triggered by stress. Early life stress in childhood has been shown to increase the likelihood of migraine in adulthood in humans. Calcitonin-gene relate peptide (CGRP) has been shown to reliably and acutely induce migraine or migraine-like behavior in both humans and rodent models. Here we investigate the impact of early life stress and CGRP on migraine-related neural circuitry, as well as the impact of early life stress on CGRP-mediated migraine-like activity in order to better understand the mechanisms by which early life stress predisposes neural circuitry to migraine brain activity. MethodsWe implemented an early life stress paradigm in the outbred strain of mice, CD1. We evaluated the impact of peripheral CGRP on migraine-like behavior and employed multi-site in vivo neurophysiology in freely behaving mice. A changepoint analysis was used to dissect differences in individual CGRP-induced responses. ResultsWe found that early life stress exacerbated migraine-related behavioral and network physiology. CGRP alone caused disruptions in neural oscillatory activity across a network of brain regions including the anterior cingulate cortex (ACC), amygdala (AMY), thalamus (Po, VPM, and MDthal), and parabrachial nucleus (PBN). We found that power across the network was lowered within 10 minutes of peripheral CGRP exposure, which was sustained for [~]40-50 min. Coherence was mostly disrupted in amygdalar brain region pairings, and took on a shorter timecourse, with partial rescue of these responses by migraine abortive, sumatriptan. We found that early life stress exacerbated most of these responses, especially AMY-thalamic coherence pairings, although early life stress in the absence of CGRP demonstrated no impact on the network overall. We further identified individual mice with brain-network activity hypersusceptible to migraine. ConclusionsOur findings demonstrate that early life stress confers vulnerability to migraine, simultaneously impacting behavior and brain network activity responses to peripheral CGRP.

neuroscience↗

Transcriptomic Evaluation of Stress Vulnerability Network using Single Cell RNA-Seq in mouse Prefrontal Cortex

Increased vulnerability to stress is a major risk factor for the manifestation of several mood disorders, including major depressive disorder (MDD). Despite the status of MDD as a significant donor to global disability, the complex integration of genetic and environmental factors that contribute to the behavioral display of such disorders has made a thorough understanding of related etiology elusive. Recent developments suggest that a brain-wide network approach is needed, taking into account the complex interplay of cell types spanning multiple brain regions. Single cell RNA-sequencing technologies can provide transcriptomic profiling at the single-cell level across heterogenous samples. Furthermore, we have previously used local field potential oscillations and machine learning to identify an electrical brain network that is indicative of a predisposed vulnerability state. Thus, this study combined single cell RNA-sequencing (scRNA-Seq) with electrical brain network measures of the stress-vulnerable state, providing a unique opportunity to access the relationship between stress network activity and transcriptomic changes within individual cell types. We found especially high numbers of differentially expressed genes between animals with high and low stress vulnerability brain network activity in astrocytes and glutamatergic neurons but we estimated that vulnerability network activity depends most on GABAergic neurons. High vulnerability network activity included upregulation of microglia and mitochondrial and metabolic pathways, while lower vulnerability involved synaptic regulation. Genes that were differentially regulated with vulnerability network activity significantly overlapped with genes identified as having significant SNPs by human GWAS for depression. Taken together, these data provide the gene expression architecture of a previously uncharacterized stress vulnerability brain state, enabling new understanding and intervention of predisposition to stress susceptibility. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/540705v2_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1ebe036org.highwire.dtl.DTLVardef@cd2131org.highwire.dtl.DTLVardef@13e3519org.highwire.dtl.DTLVardef@1100e62_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

A critical role for touch neurons in a skin-brain pathway for stress resilience

Social touch can act as a stress buffer, reducing behavioral and physiological responses to stressful scenarios. However, skin-brain touch pathways that promote stress resilience remain unknown. Here, we show that mice with an early life genetic ablation of Mrgprb4-lineage touch neurons display stress vulnerability behaviors in adulthood. Chemogenetic activation of these touch neurons reduced corticosterone levels under mild acute stress conditions. In addition, whole-brain c-Fos activity mapping while chemogenetically turning on these neurons uncovered differential neural activity patterns in brain areas relevant to somatosensation, reward, and affect. To gain mechanistic insight into this skin-brain touch pathway for stress susceptibility, we used multi-circuit neurophysiological recordings across seven brain regions at baseline and after stress in mice that had Mrgprb4-lineage touch neurons ablated in early life. Interestingly, the Mrgprb4-lineage neuron-ablated mice have alterations in local field potential phase directionality and power in the theta frequencies in mesolimbic reward regions, which may underlie our observed stress susceptibility phenotype. Together, these studies revealed that sensory neurons in the skin engage networks across the brain to promote stress resilience.

neuroscience↗