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ENeuro Jan 2024The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an...
The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in their connection strength with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS and, as a result, exert distinct influences on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution of striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1 in male and female mice and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex vivo patch clamp electrophysiology. We found that M1 and S1 dually innervate SPNs and FSIs; however, there is a consistent bias towards the M1 input in SPNs that is not found in FSIs. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPN and FSI dendrites. Notably, closely localized M1 and S1 clusters of inputs were more prevalent in SPNs than FSIs, suggesting that cortical inputs are integrated through cell-type specific mechanisms. Our results suggest that the stronger functional connectivity from M1 to SPNs compared to S1, as previously observed, is due to a higher quantity of synaptic inputs. Our results have implications for how sensorimotor integration is performed in the striatum through cell-specific differences in corticostriatal connections.
Topics: Mice; Male; Female; Animals; Vibrissae; Neurons; Interneurons; Corpus Striatum; Neostriatum
PubMed: 38164611
DOI: 10.1523/ENEURO.0503-23.2023 -
Cell Reports Jan 2024Goal-directed behaviors involve coordinated activity in many cortical areas, but whether the encoding of task variables is distributed across areas or is more...
Goal-directed behaviors involve coordinated activity in many cortical areas, but whether the encoding of task variables is distributed across areas or is more specifically represented in distinct areas remains unclear. Here, we compared representations of sensory, motor, and decision information in the whisker primary somatosensory cortex, medial prefrontal cortex, and tongue-jaw primary motor cortex in mice trained to lick in response to a whisker stimulus with mice that were not taught this association. Irrespective of learning, properties of the sensory stimulus were best encoded in the sensory cortex, whereas fine movement kinematics were best represented in the motor cortex. However, movement initiation and the decision to lick in response to the whisker stimulus were represented in all three areas, with decision neurons in the medial prefrontal cortex being more selective, showing minimal sensory responses in miss trials and motor responses during spontaneous licks. Our results reconcile previous studies indicating highly specific vs. highly distributed sensorimotor processing.
Topics: Mice; Animals; Somatosensory Cortex; Goals; Parietal Lobe; Neocortex; Neurons; Vibrissae
PubMed: 38150365
DOI: 10.1016/j.celrep.2023.113618 -
BioRxiv : the Preprint Server For... Dec 2023High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable...
High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radiofrequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Using a 14T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100×100×200μm resolution with a 2s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust BOLD responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 seconds prior to the air-puff in awake mice with repetitive stimulation, which was not detectable with the randomized stimulation paradigm. This early BC activation indicated learned anticipation through the vibrissa system and association cortices in awake mice under continuous training of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas.
PubMed: 38106227
DOI: 10.1101/2023.12.08.570803 -
Cell Reports Dec 2023Sensory cortical areas are organized into topographic maps representing the sensory epithelium. Interareal projections typically connect topographically matched...
Sensory cortical areas are organized into topographic maps representing the sensory epithelium. Interareal projections typically connect topographically matched subregions across areas. Because matched subregions process the same stimulus, their interaction is central to many computations. Here, we ask how topographically matched subregions of primary and secondary vibrissal somatosensory cortices (vS1 and vS2) interact during active touch. Volumetric calcium imaging in mice palpating an object with two whiskers revealed a sparse population of highly responsive, broadly tuned touch neurons especially pronounced in layer 2 of both areas. These rare neurons exhibited elevated synchrony and carried most touch-evoked activity in both directions. Lesioning the subregion of either area responding to the spared whiskers degraded touch responses in the unlesioned area, with whisker-specific vS1 lesions degrading whisker-specific vS2 touch responses. Thus, a sparse population of broadly tuned touch neurons dominates vS1-vS2 communication in both directions, and topographically matched vS1 and vS2 subregions recurrently amplify whisker touch activity.
Topics: Mice; Animals; Touch; Touch Perception; Neurons; Somatosensory Cortex; Vibrissae; Physical Stimulation
PubMed: 38064338
DOI: 10.1016/j.celrep.2023.113532 -
Meso-Py: Dual Brain Cortical Calcium Imaging in Mice during Head-Fixed Social Stimulus Presentation.ENeuro Dec 2023We present a cost-effective, compact foot-print, and open-source Raspberry Pi-based widefield imaging system. The compact nature allows the system to be used for...
We present a cost-effective, compact foot-print, and open-source Raspberry Pi-based widefield imaging system. The compact nature allows the system to be used for close-proximity dual-brain cortical mesoscale functional-imaging to simultaneously observe activity in two head-fixed animals in a staged social touch-like interaction. We provide all schematics, code, and protocols for a rail system where head-fixed mice are brought together to a distance where the macrovibrissae of each mouse make contact. Cortical neuronal functional signals (GCaMP6s; genetically encoded Ca sensor) were recorded from both mice simultaneously before, during, and after the social contact period. When the mice were together, we observed bouts of mutual whisking and cross-mouse correlated cortical activity across the cortex. Correlations were not observed in trial-shuffled mouse pairs, suggesting that correlated activity was specific to individual interactions. Whisking-related cortical signals were observed during the period where mice were together (closest contact). The effects of social stimulus presentation extend outside of regions associated with mutual touch and have global synchronizing effects on cortical activity.
Topics: Mice; Animals; Pregnancy; Female; Calcium; Brain; Head; Touch; Touch Perception; Vibrissae; Somatosensory Cortex
PubMed: 38053472
DOI: 10.1523/ENEURO.0096-23.2023 -
The Journal of Neuroscience : the... Jan 2024Body movements influence brain-wide neuronal activities. In the sensory cortex, thalamocortical bottom-up inputs and motor-sensory top-down inputs are thought to affect...
Body movements influence brain-wide neuronal activities. In the sensory cortex, thalamocortical bottom-up inputs and motor-sensory top-down inputs are thought to affect the dynamics of membrane potentials ( ) of neurons and change their processing of sensory information during movements. However, direct perturbation of the axons projecting to the sensory cortex from other remote areas during movements has remained unassessed, and therefore the interareal circuits generating motor-related signals in sensory cortices remain unclear. Using a -coupled opsin, eOPN3, we here inhibited interareal signals incoming to the whisker primary somatosensory barrel cortex (wS1) of awake male mice and tested their effects on whisking-related changes in neuronal activities in wS1. Spontaneous whisking in air induced the changes in spike rates of a subset of wS1 neurons, which were accompanied by depolarization and substantial reduction of slow-wave oscillatory fluctuations of Despite an extensive innervation, inhibition of inputs from the whisker primary motor cortex (wM1) to wS1 did not alter the spike rates and dynamics of wS1 neurons during whisking. In contrast, inhibition of axons from the whisker-related thalamus (wTLM) and the whisker secondary somatosensory cortex (wS2) to wS1 largely attenuated the whisking-related supra- and sub-threshold dynamics of wS1 neurons. Notably, silencing inputs from wTLM markedly decreased the modulation depth of whisking phase-tuned neurons in wS1, while inhibiting wS2 inputs did not impact the whisking variable tuning of wS1 neurons. Thus, sensorimotor integration in wS1 during spontaneous whisking is predominantly facilitated by direct synaptic inputs from wTLM and wS2 rather than from wM1.
Topics: Mice; Male; Animals; Neurons; Somatosensory Cortex; Axons; Membrane Potentials; Movement; Vibrissae
PubMed: 38050130
DOI: 10.1523/JNEUROSCI.1148-23.2023 -
The Journal of Experimental Biology Nov 2023For the two dolphin species Sotalia guianensis (Guiana dolphin) and Tursiops truncatus (bottlenose dolphin), previous research has shown that the vibrissal crypts...
For the two dolphin species Sotalia guianensis (Guiana dolphin) and Tursiops truncatus (bottlenose dolphin), previous research has shown that the vibrissal crypts located on the rostrum represent highly innervated, ampullary electroreceptors and that both species are correspondingly sensitive to weak electric fields. In the present study, for a comparative assessment of the sensitivity of the bottlenose dolphin's electroreceptive system, we determined detection thresholds for DC and AC electric fields with two bottlenose dolphins. In a psychophysical experiment, the animals were trained to respond to electric field stimuli using the go/no-go paradigm. We show that the two bottlenose dolphins are able to detect DC electric fields as low as 2.4 and 5.5 µV cm-1, respectively, a detection threshold in the same order of magnitude as those in the platypus and the Guiana dolphin. Detection thresholds for AC fields (1, 5 and 25 Hz) were generally higher than those for DC fields, and the sensitivity for AC fields decreased with increasing frequency. Although the electroreceptive sensitivity of dolphins is lower than that of elasmobranchs, it is suggested that it allows for both micro- and macro-scale orientation. In dolphins pursuing benthic foraging strategies, electroreception may facilitate short-range prey detection and target-oriented snapping of their prey. Furthermore, the ability to detect weak electric fields may enable dolphins to perceive the Earth's magnetic field through induction-based magnetoreception, thus allowing large-scale orientation.
Topics: Animals; Bottle-Nosed Dolphin; Sensation; Vibrissae
PubMed: 38035544
DOI: 10.1242/jeb.245845 -
Life (Basel, Switzerland) Nov 2023Increasing concerns about hair loss affect people's quality of life. Recent studies have found that sympathetic nerves play a positive role in regulating hair follicle...
Increasing concerns about hair loss affect people's quality of life. Recent studies have found that sympathetic nerves play a positive role in regulating hair follicle stem cell activity to promote hair growth. However, no study has investigated sympathetic innervation of transplanted follicles. Rat vibrissa follicles were extracted and implanted under the dorsal skin of BALB/c-nu/nu mice using one of two types of follicles: (1) intact follicles, where transplants included bulbs, and (2) upper follicles, where transplants excluded bulbs. Follicular samples were collected for hematoxylin and eosin staining, immunofluorescence staining for tyrosine hydroxylase (TH, a sympathetic marker) and enzyme-linked immunosorbent assays. At 37 days after implantation in both groups, follicles had entered anagen, with the growth of long hair shafts; tyrosine-hydroxylase-positive nerves were innervating follicles (1.45-fold); and norepinephrine concentrations (2.03-fold) were significantly increased compared to 5 days, but did not return to normal. We demonstrate the survival of intact and upper follicle xenografts and the partial restoration of sympathetic reinnervations of both transplanted follicles.
PubMed: 38004304
DOI: 10.3390/life13112163 -
Biomedicine & Pharmacotherapy =... Dec 2023Long-chain acylcarnitines (LCACs) are intermediates of fatty acid oxidation and are known to exert detrimental effects on mitochondria. This study aimed to test whether...
Long-chain acylcarnitines (LCACs) are intermediates of fatty acid oxidation and are known to exert detrimental effects on mitochondria. This study aimed to test whether lowering LCAC levels with the anti-ischemia compound 4-[ethyl(dimethyl)ammonio]butanoate (methyl-GBB) protects brain mitochondrial function and improves neurological outcomes after transient middle cerebral artery occlusion (MCAO). The effects of 14 days of pretreatment with methyl-GBB (5 mg/kg, p.o.) on brain acylcarnitine (short-, long- and medium-chain) concentrations and brain mitochondrial function were evaluated in Wistar rats. Additionally, the mitochondrial respiration and reactive oxygen species (ROS) production rates were determined using ex vivo high-resolution fluorespirometry under normal conditions, in models of ischemia-reperfusion injury (reverse electron transfer and anoxia-reoxygenation) and 24 h after MCAO. MCAO model rats underwent vibrissae-evoked forelimb-placing and limb-placing tests to assess neurological function. The infarct volume was measured on day 7 after MCAO using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Treatment with methyl-GBB significantly reduced the LCAC content in brain tissue, which decreased the ROS production rate without affecting the respiration rate, indicating an increase in mitochondrial coupling. Furthermore, methyl-GBB treatment protected brain mitochondria against anoxia-reoxygenation injury. In addition, treatment with methyl-GBB significantly reduced the infarct size and improved neurological outcomes after MCAO. Increased mitochondrial coupling efficiency may be the basis for the neuroprotective effects of methyl-GBB. This study provides evidence that maintaining brain energy metabolism by lowering the levels of LCACs protects against ischemia-induced brain damage in experimental stroke models.
Topics: Rats; Animals; Rats, Wistar; Reactive Oxygen Species; Mitochondria; Brain; Brain Ischemia; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Hypoxia; Reperfusion Injury
PubMed: 37924790
DOI: 10.1016/j.biopha.2023.115803 -
Nature Communications Sep 2023To localize objects during active sensing, animals must differentiate stimuli caused by volitional movement from real-world object motion. To determine a neural basis...
To localize objects during active sensing, animals must differentiate stimuli caused by volitional movement from real-world object motion. To determine a neural basis for this ability, we examined the mouse superior colliculus (SC), which contains multiple egocentric maps of sensorimotor space. By placing mice in a whisker-guided virtual reality, we discovered a rapidly adapting tactile response that transiently emerged during externally generated gains in whisker contact. Responses to self-generated touch that matched self-generated history were significantly attenuated, revealing that transient response magnitude is controlled by sensorimotor predictions. The magnitude of the transient response gradually decreased with repetitions in external motion, revealing a slow habituation based on external history. The direction of external motion was accurately encoded in the firing rates of transiently responsive neurons. These data reveal that whisker-specific adaptation and sensorimotor predictions in SC neurons enhance the localization of unexpected, externally generated changes in tactile space.
Topics: Mice; Animals; Touch; Touch Perception; Neurons; Motion; Movement; Vibrissae
PubMed: 37777516
DOI: 10.1038/s41467-023-41755-z