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PloS One 2021Obesity arising from excessive dietary fat intake is a risk factor for cognitive decline, dementia and neurodegenerative diseases, including Alzheimer's disease. Here,...
Obesity arising from excessive dietary fat intake is a risk factor for cognitive decline, dementia and neurodegenerative diseases, including Alzheimer's disease. Here, we studied the effect of long-term high-fat diet (HFD) (24 weeks) and return to normal diet (ND) on behavioral features, microglia and neurons in adult male C57BL/6J mice. Consequences of HFD-induced obesity and dietary changes on general health (coat appearance, presence of vibrissae), sensory and motor reflexes, learning and memory were assessed by applying a phenotypic assessment protocol, the Y maze and Morris Water Maze test. Neurons and microglia were histologically analyzed within the mediobasal hypothalamus, hippocampus and frontal motor cortex after long-term HFD and change of diet. Long periods of HFD caused general health issues (coat alterations, loss of vibrissae), but did not affect sensory and motor reflexes, emotional state, memory and learning. Long-term HFD increased the microglial response (increased Iba1 fluorescence intensity, percentage of Iba1-stained area and Iba1 gene expression) within the hypothalamus, but not in the cortex and hippocampus. In neither of these regions, neurodegeneration or intracellular lipid droplet accumulation was observed. The former alterations were reversible in mice whose diet was changed from HFD to ND. Taken together, long periods of excessive dietary fat alone do not cause learning deficits or spatial memory impairment, though HFD-induced obesity may have detrimental consequences for cognitive flexibility. Our data confirm the selective responsiveness of hypothalamic microglia to HFD.
Topics: Animals; Calcium-Binding Proteins; Cerebral Cortex; Cognitive Dysfunction; Diet, High-Fat; Disease Models, Animal; Hippocampus; Male; Maze Learning; Mice; Mice, Inbred C57BL; Microfilament Proteins; Morris Water Maze Test; Obesity; Spatial Memory
PubMed: 34587222
DOI: 10.1371/journal.pone.0257921 -
The Journal of Neuroscience : the... Mar 2022Lateralization is a hallmark of somatosensory processing in the mammalian brain. However, in addition to their contralateral representation, unilateral tactile stimuli...
Lateralization is a hallmark of somatosensory processing in the mammalian brain. However, in addition to their contralateral representation, unilateral tactile stimuli also modulate neuronal activity in somatosensory cortices of the ipsilateral hemisphere. The cellular organization and functional role of these ipsilateral stimulus responses in awake somatosensory cortices, especially regarding stimulus coding, are unknown. Here, we targeted silicon probe recordings to the vibrissa region of primary (S1) and secondary (S2) somatosensory cortex of awake head-fixed mice of either sex while delivering ipsilateral and contralateral whisker stimuli. Ipsilateral stimuli drove larger and more reliable responses in S2 than in S1, and activated a larger fraction of stimulus-responsive neurons. Ipsilateral stimulus-responsive neurons were rare in layer 4 of S1, but were located in equal proportion across all layers in S2. Linear classifier analyses further revealed that decoding of the ipsilateral stimulus was more accurate in S2 than S1, whereas S1 decoded contralateral stimuli most accurately. These results reveal substantial encoding of ipsilateral stimuli in S1 and especially S2, consistent with the hypothesis that higher cortical areas may integrate tactile inputs across larger portions of space, spanning both sides of the body. Tactile information obtained by one side of the body is represented in the activity of neurons of the opposite brain hemisphere. However, unilateral tactile stimulation also modulates neuronal activity in the other, or ipsilateral, brain hemisphere. This ipsilateral activity may play an important role in the representation and processing of tactile information, in particular when the sense of touch involves both sides of the body. Our work in the whisker system of awake mice reveals that neocortical ipsilateral activity, in particular that of deep layer excitatory neurons of secondary somatosensory cortex (S2), contains information about the presence and the velocity of unilateral tactile stimuli, which supports a key role for S2 in integrating tactile information across both body sides.
Topics: Animals; Mammals; Mice; Somatosensory Cortex; Touch; Touch Perception; Vibrissae; Wakefulness
PubMed: 35135855
DOI: 10.1523/JNEUROSCI.1417-21.2022 -
Proceedings of the National Academy of... Jan 2021Activity of sensory and motor cortices is essential for sensorimotor integration. In particular, coherence between these areas may indicate binding of critical functions...
Activity of sensory and motor cortices is essential for sensorimotor integration. In particular, coherence between these areas may indicate binding of critical functions like perception, motor planning, action, or sleep. Evidence is accumulating that cerebellar output modulates cortical activity and coherence, but how, when, and where it does so is unclear. We studied activity in and coherence between S1 and M1 cortices during whisker stimulation in the absence and presence of optogenetic Purkinje cell stimulation in crus 1 and 2 of awake mice, eliciting strong simple spike rate modulation. Without Purkinje cell stimulation, whisker stimulation triggers fast responses in S1 and M1 involving transient coherence in a broad spectrum. Simultaneous stimulation of Purkinje cells and whiskers affects amplitude and kinetics of sensory responses in S1 and M1 and alters the estimated S1-M1 coherence in theta and gamma bands, allowing bidirectional control dependent on behavioral context. These effects are absent when Purkinje cell activation is delayed by 20 ms. Focal stimulation of Purkinje cells revealed site specificity, with cells in medial crus 2 showing the most prominent and selective impact on estimated coherence, i.e., a strong suppression in the gamma but not the theta band. Granger causality analyses and computational modeling of the involved networks suggest that Purkinje cells control S1-M1 phase consistency predominantly via ventrolateral thalamus and M1. Our results indicate that activity of sensorimotor cortices can be dynamically and functionally modulated by specific cerebellar inputs, highlighting a widespread role of the cerebellum in coordinating sensorimotor behavior.
Topics: Animals; Cerebellar Cortex; Cerebellum; Female; Humans; Male; Mice; Mice, Transgenic; Motor Cortex; Optogenetics; Purkinje Cells; Sensorimotor Cortex; Somatosensory Cortex; Ventral Thalamic Nuclei; Vibrissae
PubMed: 33443203
DOI: 10.1073/pnas.2015292118 -
Journal of the Royal Society, Interface Oct 2021Seals are known to use their highly sensitive whiskers to precisely follow the hydrodynamic trail left behind by prey. Studies estimate that a seal can track a herring... (Review)
Review
Seals are known to use their highly sensitive whiskers to precisely follow the hydrodynamic trail left behind by prey. Studies estimate that a seal can track a herring that is swimming as far as 180 m away, indicating an incredible detection apparatus on a par with the echolocation system of dolphins and porpoises. This remarkable sensing capability is enabled by the unique undulating structural morphology of the whisker that suppresses vortex-induced vibrations (VIVs) and thus increases the signal-to-noise ratio of the flow-sensing whiskers. In other words, the whiskers vibrate minimally owing to the seal's swimming motion, eliminating most of the self-induced noise and making them ultrasensitive to the vortices in the wake of escaping prey. Because of this impressive ability, the seal whisker has attracted much attention in the scientific community, encompassing multiple fields of sensory biology, fluid mechanics, biomimetic flow sensing and soft robotics. This article presents a comprehensive review of the seal whisker literature, covering the behavioural experiments on real seals, VIV suppression capabilities enabled by the undulating geometry, wake vortex-sensing mechanisms, morphology and material properties and finally engineering applications inspired by the shape and functionality of seal whiskers. Promising directions for future research are proposed.
Topics: Animals; Biomimetics; Hydrodynamics; Motion; Vibration; Vibrissae
PubMed: 34699729
DOI: 10.1098/rsif.2021.0629 -
Neuron Sep 2022The thalamus controls transmission of sensory signals from periphery to cortex, ultimately shaping perception. Despite this significant role, dynamic thalamic gating and...
The thalamus controls transmission of sensory signals from periphery to cortex, ultimately shaping perception. Despite this significant role, dynamic thalamic gating and the consequences for downstream cortical sensory representations have not been well studied in the awake brain. We optogenetically modulated the ventro-posterior-medial thalamus in the vibrissa pathway of the awake mouse and measured spiking activity in the thalamus and activity in primary somatosensory cortex (S1) using extracellular electrophysiology and genetically encoded voltage imaging. Thalamic hyperpolarization significantly enhanced thalamic sensory-evoked bursting; however, surprisingly, the S1 cortical response was not amplified, but instead, timing precision was significantly increased, spatial activation more focused, and there was an increased synchronization of cortical inhibitory neurons. A thalamocortical network model implicates the modulation of precise timing of feedforward thalamic population spiking, presenting a highly sensitive, timing-based gating of sensory signaling to the cortex.
Topics: Animals; Mice; Neurons; Signal Transduction; Somatosensory Cortex; Thalamus; Wakefulness
PubMed: 35803270
DOI: 10.1016/j.neuron.2022.06.008 -
Neuron May 2020To interpret the environment, our brain must evaluate external stimuli against internal representations from past experiences. How primary (S1) and secondary (S2)...
To interpret the environment, our brain must evaluate external stimuli against internal representations from past experiences. How primary (S1) and secondary (S2) somatosensory cortices process stimuli depending on recent experiences is unclear. Using simultaneous multi-area population imaging of projection neurons and focal optogenetic inactivation, we studied mice performing a whisker-based working memory task. We find that activity reflecting a current stimulus, the recollection of a previous stimulus (cued recall), and the stimulus category are distributed across S1 and S2. Despite this overlapping representation, S2 is important for processing cued recall responses and transmitting these responses to S1. S2 network properties differ from S1, wherein S2 persistently encodes cued recall and the stimulus category under passive conditions. Although both areas encode the stimulus category, only information in S1 is important for task performance through pathways that do not necessarily include S2. These findings reveal both distributed and segregated roles for S1 and S2 in context-dependent sensory processing.
Topics: Animals; Male; Memory, Short-Term; Mice; Models, Neurological; Neurons; Somatosensory Cortex; Touch Perception; Vibrissae
PubMed: 32164873
DOI: 10.1016/j.neuron.2020.02.004 -
The Journal of Comparative Neurology Jun 2021Barrel subfields in rodent primary somatosensory cortex (SI) are important model systems for studying cortical organization and reorganization. During cortical...
Barrel subfields in rodent primary somatosensory cortex (SI) are important model systems for studying cortical organization and reorganization. During cortical reorganization that follows limb deafferentation, neurons in deafferented forelimb SI become responsive to previously unexpressed inputs from the lower jaw. Although the lower jaw barrel subfield (LJBSF) is a likely source of the input, this subfield has received little attention. Our aim was to describe the structural and functional organization of the normal LJBSF. To investigate LJBSF organization, a nomenclature for lower jaw skin surface was developed, cytochrome oxidase (CO) was used to label flattened-cut LJBSF sections, microelectrodes were used to map the lower jaw skin surface representation in SI, and electrolytic lesions, recovered from electrode penetrations, were used to align the physiological map to the underlying barrel map. LJBSF is a tear-shaped subfield containing approximately 24 barrels, arranged in eight mediolateral rows and a barrel-free zone capping the anterior border. The representation of the lower jaw skin consisting of chin vibrissae and microvibrissae embedded in common fur is somatotopically organized in a single map in the contralateral SI. This physiological map shows that the activity from the vibrissae aligns with the CO-staining of the underlying LJBSF. LJBSF barrels receive topographically ordered barrel-specific input from individual vibrissa and microvibrissae in the lower jaw but not from trident whiskers. The barrel-free zone receives topographically ordered input from the lower lip. These data demonstrating that the LJBSF is a highly organized subfield are essential for understanding its possible role in cortical reorganization.
Topics: Animals; Brain Mapping; Female; Jaw; Neurons; Rats; Rats, Sprague-Dawley; Somatosensory Cortex; Vibrissae
PubMed: 33135168
DOI: 10.1002/cne.25063 -
Nature Communications Apr 2023Suppressing responses to distractor stimuli is a fundamental cognitive function, essential for performing goal-directed tasks. A common framework for the neuronal...
Suppressing responses to distractor stimuli is a fundamental cognitive function, essential for performing goal-directed tasks. A common framework for the neuronal implementation of distractor suppression is the attenuation of distractor stimuli from early sensory to higher-order processing. However, details of the localization and mechanisms of attenuation are poorly understood. We trained mice to selectively respond to target stimuli in one whisker field and ignore distractor stimuli in the opposite whisker field. During expert task performance, optogenetic inhibition of whisker motor cortex increased the overall tendency to respond and the detection of distractor whisker stimuli. Within sensory cortex, optogenetic inhibition of whisker motor cortex enhanced the propagation of distractor stimuli into target-preferring neurons. Single unit analyses revealed that whisker motor cortex (wMC) decorrelates target and distractor stimulus encoding in target-preferring primary somatosensory cortex (S1) neurons, which likely improves selective target stimulus detection by downstream readers. Moreover, we observed proactive top-down modulation from wMC to S1, through the differential activation of putative excitatory and inhibitory neurons before stimulus onset. Overall, our studies support a contribution of motor cortex to sensory selection, in suppressing behavioral responses to distractor stimuli by gating distractor stimulus propagation within sensory cortex.
Topics: Mice; Animals; Somatosensory Cortex; Motor Cortex; Parietal Lobe; Neurons; Vibrissae
PubMed: 37055425
DOI: 10.1038/s41467-023-37848-4 -
The Journal of Neuroscience : the... Oct 2020The amyloid-β (Aβ) peptide, a key pathogenic factor in Alzheimer's disease, attenuates the increase in cerebral blood flow (CBF) evoked by neural activity (functional...
The amyloid-β (Aβ) peptide, a key pathogenic factor in Alzheimer's disease, attenuates the increase in cerebral blood flow (CBF) evoked by neural activity (functional hyperemia), a vital homeostatic response in which NMDA receptors (NMDARs) play a role through nitric oxide, and the CBF increase produced by endothelial factors. Tissue plasminogen activator (tPA), which is reduced in Alzheimer's disease and in mouse models of Aβ accumulation, is required for the full expression of the NMDAR-dependent component of functional hyperemia. Therefore, we investigated whether tPA is involved in the neurovascular dysfunction of Aβ. tPA activity was reduced, and the tPA inhibitor plasminogen inhibitor-1 (PAI-1) was increased in male mice expressing the Swedish mutation of the amyloid precursor protein (tg2576). Counteracting the tPA reduction with exogenous tPA or with pharmacological inhibition or genetic deletion of PAI-1 completely reversed the attenuation of the CBF increase evoked by whisker stimulation but did not ameliorate the response to the endothelium-dependent vasodilator acetylcholine. The tPA deficit attenuated functional hyperemia by suppressing NMDAR-dependent nitric oxide production during neural activity. Pharmacological inhibition of PAI-1 increased tPA activity, prevented neurovascular uncoupling, and ameliorated cognition in 11- to 12-month-old tg2576 mice, effects associated with a reduction of cerebral amyloid angiopathy but not amyloid plaques. The data unveil a selective role of the tPA in the suppression of functional hyperemia induced by Aβ and in the mechanisms of cerebral amyloid angiopathy, and support the possibility that modulation of the PAI-1-tPA pathway may be beneficial in diseases associated with amyloid accumulation. Amyloid-β (Aβ) peptides have profound neurovascular effects that may contribute to cognitive impairment in Alzheimer's disease. We found that Aβ attenuates the increases in blood flow evoked by neural activation through a reduction in tissue plasminogen activator (tPA) caused by upregulation of its endogenous inhibitor plasminogen inhibitor-1 (PAI-1). tPA deficiency prevents NMDA receptors from triggering nitric oxide production, thereby attenuating the flow increase evoked by neural activity. PAI-1 inhibition restores tPA activity, rescues neurovascular coupling, reduces amyloid deposition around blood vessels, and improves cognition in a mouse model of Aβ accumulation. The findings demonstrate a previously unappreciated role of tPA in Aβ-related neurovascular dysfunction and in vascular amyloid deposition. Restoration of tPA activity could be of therapeutic value in diseases associated with amyloid accumulation.
Topics: Amyloid beta-Protein Precursor; Animals; Blood Vessels; Cerebral Amyloid Angiopathy; Cerebrovascular Circulation; Cerebrovascular Disorders; Cognition; Humans; Hyperemia; Male; Mice; Mice, Knockout; Mice, Transgenic; Neurons; Nitric Oxide; Physical Stimulation; Receptors, N-Methyl-D-Aspartate; Serpin E2; Tissue Plasminogen Activator; Vibrissae
PubMed: 32928888
DOI: 10.1523/JNEUROSCI.1140-20.2020 -
Anatomical Record (Hoboken, N.J. : 2007) Jan 2020While most mammals have whiskers, some tactile specialists-mainly small, nocturnal, and arboreal species-can actively move their whiskers in a symmetrical, cyclic...
While most mammals have whiskers, some tactile specialists-mainly small, nocturnal, and arboreal species-can actively move their whiskers in a symmetrical, cyclic movement called whisking. Whisking enables mammals to rapidly, tactually scan their environment to efficiently guide locomotion and foraging in complex habitats. The muscle architecture that enables whisking is preserved from marsupials to primates, prompting researchers to suggest that a common ancestor might have had moveable whiskers. Studying the evolution of whisker touch sensing is difficult, and we suggest that measuring an aspect of skull morphology that correlates with whisking would enable comparisons between extinct and extant mammals. We find that whisking mammals have larger infraorbital foramen (IOF) areas, which indicates larger infraorbital nerves and an increase in sensory acuity. While this relationship is quite variable and IOF area cannot be used to solely predict the presence of whisking, whisking mammals all have large IOF areas. Generally, this pattern holds true regardless of an animal's substrate preferences or activity patterns. Data from fossil mammals and ancestral character state reconstruction and tracing techniques for extant mammals suggest that whisking is not the ancestral state for therian mammals. Instead, whisking appears to have evolved independently as many as seven times across the clades Marsupialia, Afrosoricida, Eulipotyphla, and Rodentia, with Xenarthra the only placental superordinal clade lacking whisking species. However, the term whisking only captures symmetrical and rhythmic movements of the whiskers, rather than all possible whisker movements, and early mammals may still have had moveable whiskers. Anat Rec, 2018. © 2018 American Association for Anatomy.
Topics: Animals; Behavior, Animal; Biological Evolution; Biomechanical Phenomena; Locomotion; Mammals; Somatosensory Cortex; Vibration; Vibrissae
PubMed: 30332721
DOI: 10.1002/ar.23989