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Progress in Neuro-psychopharmacology &... May 2024Early life stress may induce synaptic changes within brain regions associated with behavioral disorders. Here, we investigated glutamatergic functional connectivity by a...
Early life stress may induce synaptic changes within brain regions associated with behavioral disorders. Here, we investigated glutamatergic functional connectivity by a postsynaptic density immediate-early gene-based network analysis. Pregnant female Sprague-Dawley rats were randomly divided into two experimental groups: one exposed to stress sessions and the other serving as a stress-free control group. Homer1 expression was evaluated by in situ hybridization technique in eighty-eight brain regions of interest of male rat offspring. Differences between the perinatal stress exposed group (PRS) (n = 5) and the control group (CTR) (n = 5) were assessed by performing the Student's t-test via SPSS 28.0.1.0 with Bonferroni correction. Additionally, all possible pairwise Spearman's correlations were computed as well as correlation matrices and networks for each experimental group were generated via RStudio and Cytoscape. Perinatal stress exposure was associated with Homer1a induction in several cortical, thalamic, and striatal regions. Furthermore, it was found to affect functional connectivity between the lateral septal nucleus and central medial thalamic nucleus; retrosplenial granular b cortex and the anterior part of the paraventricular thalamic nucleus; and between the anterior part of the paraventricular thalamic nucleus and prefrontal cortex, amygdaloid nuclei, and hippocampal regions. Finally, the study of networks showed a significant reduction in multiple connections for the ventrolateral part of the anteroventral thalamic nucleus after perinatal stress exposure, as well as a decrease in the centrality of ventral anterior thalamic and amygdaloid nuclei. Within the present preclinical setting, perinatal stress exposure is a modifier of glutamatergic early gene-based functional connectivity in neuronal circuits involved in behaviors relevant to model neurodevelopmental disorders.
PubMed: 38762163
DOI: 10.1016/j.pnpbp.2024.111032 -
BioRxiv : the Preprint Server For... Apr 2024Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human...
Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human health and disease. The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are key thalamic nuclei involved in the processing and relay of auditory and visual information, respectively, and are the subject of blood-oxygen-level-dependent (BOLD) fMRI studies of neural activation and functional connectivity in human participants. However, localization of BOLD fMRI signal originating from neural activity in MGN and LGN remains a technical challenge, due in part to the poor definition of boundaries of these thalamic nuclei in standard T1-weighted and T2-weighted magnetic resonance imaging sequences. Here, we report the development and evaluation of an auditory and visual sensory thalamic localizer (TL) fMRI task that produces participant-specific functionally-defined regions of interest (fROIs) of both MGN and LGN, using 3 Tesla multiband fMRI and a clustered-sparse temporal acquisition sequence, in less than 16 minutes of scan time. We demonstrate the use of MGN and LGN fROIs obtained from the TL fMRI task in standard resting-state functional connectivity (RSFC) fMRI analyses in the same participants. In RSFC analyses, we validated the specificity of MGN and LGN fROIs for signals obtained from primary auditory and visual cortex, respectively, and benchmark their performance against alternative atlas- and segmentation-based localization methods. The TL fMRI task and analysis code (written in Presentation and MATLAB, respectively) have been made freely available to the wider research community.
PubMed: 38746171
DOI: 10.1101/2024.04.28.591516 -
PLoS Biology May 2024The processing of sensory information, even at early stages, is influenced by the internal state of the animal. Internal states, such as arousal, are often characterized...
The processing of sensory information, even at early stages, is influenced by the internal state of the animal. Internal states, such as arousal, are often characterized by relating neural activity to a single "level" of arousal, defined by a behavioral indicator such as pupil size. In this study, we expand the understanding of arousal-related modulations in sensory systems by uncovering multiple timescales of pupil dynamics and their relationship to neural activity. Specifically, we observed a robust coupling between spiking activity in the mouse dorsolateral geniculate nucleus (dLGN) of the thalamus and pupil dynamics across timescales spanning a few seconds to several minutes. Throughout all these timescales, 2 distinct spiking modes-individual tonic spikes and tightly clustered bursts of spikes-preferred opposite phases of pupil dynamics. This multi-scale coupling reveals modulations distinct from those captured by pupil size per se, locomotion, and eye movements. Furthermore, coupling persisted even during viewing of a naturalistic movie, where it contributed to differences in the encoding of visual information. We conclude that dLGN spiking activity is under the simultaneous influence of multiple arousal-related processes associated with pupil dynamics occurring over a broad range of timescales.
Topics: Animals; Pupil; Geniculate Bodies; Mice; Action Potentials; Arousal; Male; Mice, Inbred C57BL; Photic Stimulation; Neurons; Thalamus; Eye Movements; Time Factors; Visual Pathways
PubMed: 38743775
DOI: 10.1371/journal.pbio.3002614 -
Frontiers in Neural Circuits 2024The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The... (Comparative Study)
Comparative Study
The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.
Topics: Animals; Rats; Mice; Male; Neural Pathways; Intralaminar Thalamic Nuclei; Mice, Inbred C57BL; Rats, Sprague-Dawley; Female
PubMed: 38736977
DOI: 10.3389/fncir.2024.1384621 -
Annals of Clinical and Translational... May 2024To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo...
OBJECTIVE
To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo high-gradient diffusion MRI.
METHODS
In this cross-sectional study, 41 people with multiple sclerosis and 34 age and sex-matched healthy controls underwent 3T MRI with up to 300 mT/m gradients using a multi-shell diffusion protocol consisting of eight b-values and diffusion time of 19 ms. Each thalamus was parcellated into 25 subregions for volume determination and diffusion metric estimation. The soma and neurite density imaging model was applied to obtain estimates of intra-neurite, intra-soma, and extra-cellular signal fractions for each subregion and within structurally connected white matter trajectories and cortex.
RESULTS
Multiple sclerosis-related volume loss was more pronounced in posterior/medial subregions than anterior/ventral subregions. Intra-soma signal fraction was lower in multiple sclerosis, reflecting reduced cell body density, while the extra-cellular signal fraction was higher, reflecting greater extra-cellular space, both of which were observed more in posterior/medial subregions than anterior/ventral subregions. Lower intra-neurite signal fraction in connected normal-appearing white matter and lower intra-soma signal fraction of structurally connected cortex were associated with reduced subregional thalamic volumes. Intrinsic and extrinsic microstructural measures independently related to subregional volume with heterogeneity across atrophy-prone thalamic nuclei. Extrinsic microstructural alterations predicted left anteroventral, intrinsic microstructural alterations predicted bilateral medial pulvinar, and both intrinsic and extrinsic factors predicted lateral geniculate and medial mediodorsal volumes.
INTERPRETATION
Our results might be reflective of the involvement of anterograde and retrograde degeneration from white matter demyelination and cerebrospinal fluid-mediated damage in subregional thalamic volume loss.
PubMed: 38725151
DOI: 10.1002/acn3.52026 -
Nature Communications May 2024The neural basis of fear of heights remains largely unknown. In this study, we investigated the fear response to heights in male mice and observed characteristic...
The neural basis of fear of heights remains largely unknown. In this study, we investigated the fear response to heights in male mice and observed characteristic aversive behaviors resembling human height vertigo. We identified visual input as a critical factor in mouse reactions to heights, while peripheral vestibular input was found to be nonessential for fear of heights. Unexpectedly, we found that fear of heights in naïve mice does not rely on image-forming visual processing by the primary visual cortex. Instead, a subset of neurons in the ventral lateral geniculate nucleus (vLGN), which connects to the lateral/ventrolateral periaqueductal gray (l/vlPAG), drives the expression of fear associated with heights. Additionally, we observed that a subcortical visual pathway linking the superior colliculus to the lateral posterior thalamic nucleus inhibits the defensive response to height threats. These findings highlight a rapid fear response to height threats through a subcortical visual and defensive pathway from the vLGN to the l/vlPAG.
Topics: Animals; Male; Fear; Mice; Geniculate Bodies; Superior Colliculi; Mice, Inbred C57BL; Visual Pathways; Periaqueductal Gray; Neurons; Primary Visual Cortex; Visual Perception; Behavior, Animal
PubMed: 38702319
DOI: 10.1038/s41467-024-48147-x -
Journal of Neural Engineering May 2024Deep brain stimulation (DBS) is a therapy for Parkinson's disease (PD) and essential tremor (ET). The mechanism of action of DBS is still incompletely understood....
Deep brain stimulation (DBS) is a therapy for Parkinson's disease (PD) and essential tremor (ET). The mechanism of action of DBS is still incompletely understood. Retrospective group analysis of intra-operative data recorded from ET patients implanted in the ventral intermediate nucleus of the thalamus (Vim) is rare. Intra-operative stimulation tests generate rich data and their use in group analysis has not yet been explored.To implement, evaluate, and apply a group analysis workflow to generate probabilistic stimulation maps (PSMs) using intra-operative stimulation data from ET patients implanted in Vim.A group-specific anatomical template was constructed based on the magnetic resonance imaging scans of 6 ET patients and 13 PD patients. Intra-operative test data (total:= 1821) from the 6 ET patients was analyzed: patient-specific electric field simulations together with tremor assessments obtained by a wrist-based acceleration sensor were transferred to this template. Occurrence and weighted mean maps were generated. Voxels associated with symptomatic response were identified through a linear mixed model approach to form a PSM. Improvements predicted by the PSM were compared to those clinically assessed. Finally, the PSM clusters were compared to those obtained in a multicenter study using data from chronic stimulation effects in ET.Regions responsible for improvement identified on the PSM were in the posterior sub-thalamic area (PSA) and at the border between the Vim and ventro-oral nucleus of the thalamus (VO). The comparison with literature revealed a center-to-center distance of less than 5 mm and an overlap score (Dice) of 0.4 between the significant clusters. Our workflow and intra-operative test data from 6 ET-Vim patients identified effective stimulation areas in PSA and around Vim and VO, affirming existing medical literature.This study supports the potential of probabilistic analysis of intra-operative stimulation test data to reveal DBS's action mechanisms and to assist surgical planning.
Topics: Humans; Essential Tremor; Deep Brain Stimulation; Female; Male; Aged; Middle Aged; Thalamus; Brain Mapping; Retrospective Studies; Magnetic Resonance Imaging; Ventral Thalamic Nuclei; Parkinson Disease; Intraoperative Neurophysiological Monitoring
PubMed: 38701768
DOI: 10.1088/1741-2552/ad4742 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Apr 2024Temporal interference (TI) as a new neuromodulation technique can be applied to non-invasive deep brain stimulation. In order to verify its effectiveness in the...
Temporal interference (TI) as a new neuromodulation technique can be applied to non-invasive deep brain stimulation. In order to verify its effectiveness in the regulation of motor behavior in animals, this paper uses the TI method to focus the envelope electric field to the ventral posterior lateral nucleus (VPL) of the thalamus in the deep brain of mouse to regulate left- and right-turning motor behavior. The focusability of TI in the mouse VPL was analyzed by finite element method, and the focus area and volume were obtained by numerical calculation. A stimulator was used to generate TI current to stimulate the mouse VPL to verify the effectiveness of the TI stimulation method, and the accuracy of the focus location was further determined by c-Fos immunofluorescence experiments. The results showed that the electric field generated by TI stimulation was able to focus on the VPL nuclei when the stimulation current reached 800 μA; the mouse were able to make corresponding left and right turns according to the stimulation position; and the c-Fos positive cell markers in the VPL nuclei increased significantly after stimulation. This study confirms the feasibility of TI in regulating animal motor behavior and provides a non-invasive stimulation method for brain tissue for animal robots.
Topics: Animals; Mice; Deep Brain Stimulation; Motor Activity; Proto-Oncogene Proteins c-fos; Behavior, Animal; Ventral Thalamic Nuclei; Finite Element Analysis
PubMed: 38686416
DOI: 10.7507/1001-5515.202305032 -
Brain Stimulation 2024
Letter of response to "concerns about efficacy of deep brain stimulation (DBS) in centromedian-parafascicular thalamic complex for rapid onset dystonia-parkinsonism (DYT12-ATP1A3)".
Topics: Deep Brain Stimulation; Humans; Dystonic Disorders; Parkinsonian Disorders; Intralaminar Thalamic Nuclei
PubMed: 38685262
DOI: 10.1016/j.brs.2024.02.015 -
Brain Stimulation 2024
Topics: Deep Brain Stimulation; Humans; Dystonic Disorders; Intralaminar Thalamic Nuclei; Parkinsonian Disorders; Sodium-Potassium-Exchanging ATPase
PubMed: 38685261
DOI: 10.1016/j.brs.2024.02.008