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Scientific Reports Mar 2024The pathophysiology underlying the post-acute sequelae of COVID-19 remains understudied and poorly understood, particularly in healthy adults with a history of mild...
The pathophysiology underlying the post-acute sequelae of COVID-19 remains understudied and poorly understood, particularly in healthy adults with a history of mild infection. Chronic neuroinflammation may underlie these enduring symptoms, but studying neuroinflammatory phenomena in vivo is challenging, especially without a comparable pre-COVID-19 dataset. In this study, we present a unique dataset of 10 otherwise healthy individuals scanned before and after experiencing mild COVID-19. Two emerging MR-based methods were used to map pre- to post-COVID-19 brain temperature and free water changes. Post-COVID-19 brain temperature and free water increases, which are indirect biomarkers of neuroinflammation, were found in structures functionally associated with olfactory, cognitive, and memory processing. The largest pre- to post-COVID brain temperature increase was observed in the left olfactory tubercle (p = 0.007, 95% CI [0.48, 3.01]), with a mean increase of 1.75 °C. Notably, the olfactory tubercle is also the region of the primary olfactory cortex where participants with chronic olfactory dysfunction showed the most pronounced increases as compared to those without lingering olfactory dysfunction (adjusted p = 0.0189, 95% CI [1.42, 5.27]). These preliminary insights suggest a potential link between neuroinflammation and chronic cognitive and olfactory dysfunction following mild COVID-19, although further investigations are needed to improve our understanding of what underlies these phenomena.
Topics: Adult; Humans; Neuroinflammatory Diseases; Temperature; COVID-19; Brain; Olfaction Disorders; Water
PubMed: 38548815
DOI: 10.1038/s41598-024-57561-6 -
The Journal of Neuroscience : the... May 2020Rodents can successfully learn multiple novel stimulus-response associations after only a few repetitions when the contingencies predict reward. The circuits modified...
Rodents can successfully learn multiple novel stimulus-response associations after only a few repetitions when the contingencies predict reward. The circuits modified during such reinforcement learning to support decision-making are not known, but the olfactory tubercle (OT) and posterior piriform cortex (pPC) are candidates for decoding reward category from olfactory sensory input and relaying this information to cognitive and motor areas. Through single-cell recordings in behaving male and female C57BL/6 mice, we show here that an explicit representation for reward category emerges in the OT within minutes of learning a novel odor-reward association, whereas the pPC lacks an explicit representation even after weeks of overtraining. The explicit reward category representation in OT is visible in the first sniff (50-100 ms) of an odor on each trial, and precedes the motor action. Together, these results suggest that the coding of stimulus information required for reward prediction does not occur within olfactory cortex, but rather in circuits involving the olfactory striatum. Rodents are olfactory specialists and can use odors to learn contingencies quickly and well. We have found that mice can readily learn to place multiple odors into rewarded and unrewarded categories. Once they have learned the rule, they can do such categorization in a matter of minutes (<10 trials). We found that neural activity in olfactory cortex largely reflects sensory coding, with very little explicit information about categories. By contrast, neural activity in a brain region in the ventral striatum is rapidly modified in a matter of minutes to reflect reward category. Our experiments set up a paradigm for studying rapid sensorimotor reinforcement in a circuit that is right at the interface of sensory input and reward areas.
Topics: Animals; Female; Male; Mice; Mice, Inbred C57BL; Neurons; Olfactory Perception; Olfactory Tubercle; Piriform Cortex; Reward
PubMed: 32321744
DOI: 10.1523/JNEUROSCI.2604-19.2020 -
IBRO Reports Dec 2020The tenia tecta is extensively interconnected with the main olfactory bulb and olfactory cortical areas and is well positioned to contribute to olfactory processing....
The tenia tecta is extensively interconnected with the main olfactory bulb and olfactory cortical areas and is well positioned to contribute to olfactory processing. However, little is known about odor representation within its dorsal (DTT) and ventral (VTT) components. To address this need, spontaneous and odor-evoked activity of DTT and VTT neurons was recorded from urethane anesthetized mice and compared to activity recorded from adjacent areas within adjacent caudomedial aspects of the anterior olfactory nucleus (AON). Neurons recorded from DTT, VTT, and AON exhibited odor-selective alterations in firing rate in response to a diverse set of monomolecular odorants. While DTT and AON neurons exhibited similar tuning breadth, selectivity, and response topography, the proportion of odor-selective neurons was substantially higher in the DTT. These findings provide evidence that the tenia tecta may contribute to the encoding of specific stimulus attributes. Further work is needed to fully characterize functional organization of the tenia tecta and its contribution to sensory representation and utilization.
PubMed: 32793841
DOI: 10.1016/j.ibror.2020.07.010 -
Progress in Neurobiology Jun 2021During mammalian evolution, primate neocortex expanded, shifting hippocampal functional networks away from primary sensory cortices, towards association cortices....
During mammalian evolution, primate neocortex expanded, shifting hippocampal functional networks away from primary sensory cortices, towards association cortices. Reflecting this rerouting, human resting hippocampal functional networks preferentially include higher association cortices, while those in rodents retained primary sensory cortices. Research on human visual, auditory and somatosensory systems shows evidence of this rerouting. Olfaction, however, is unique among sensory systems in its relative structural conservation throughout mammalian evolution, and it is unknown whether human primary olfactory cortex was subject to the same rerouting. We combined functional neuroimaging and intracranial electrophysiology to directly compare hippocampal functional networks across human sensory systems. We show that human primary olfactory cortex-including the anterior olfactory nucleus, olfactory tubercle and piriform cortex-has stronger functional connectivity with hippocampal networks at rest, compared to other sensory systems. This suggests that unlike other sensory systems, olfactory-hippocampal connectivity may have been retained in mammalian evolution. We further show that olfactory-hippocampal connectivity oscillates with nasal breathing. Our findings suggest olfaction might provide insight into how memory and cognition depend on hippocampal interactions.
Topics: Brain Mapping; Cerebral Cortex; Hippocampus; Humans; Olfactory Cortex; Sense Organs; Smell
PubMed: 33640412
DOI: 10.1016/j.pneurobio.2021.102027 -
BioRxiv : the Preprint Server For... Dec 2023The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Though we have identified...
The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Though we have identified many brain nuclei that play various roles in reward processing, a significant gap remains in understanding how valence encoding transforms through the layers of sensory processing. To address this gap, we carried out a comparative investigation of the olfactory tubercle (OT), and the ventral pallidum (VP) - 2 connected nuclei of the basal ganglia which have both been implicated in reward processing. First, using anterograde and retrograde tracing, we show that both D1 and D2 neurons of the OT project primarily to the VP and minimally elsewhere. Using 2-photon calcium imaging, we then investigated how the identity of the odor and reward contingency of the odor are differently encoded by neurons in either structure during a classical conditioning paradigm. We find that VP neurons robustly encode reward contingency, but not identity, in low-dimensional space. In contrast, OT neurons primarily encode odor identity in high-dimensional space. Though D1 OT neurons showed larger response vectors to rewarded odors than other odors, we propose this is better interpreted as identity encoding with enhanced contrast rather than as valence encoding. Finally, using a novel conditioning paradigm that decouples reward contingency and licking vigor, we show that both features are encoded by non-overlapping VP neurons. These results provide a novel framework for the striatopallidal circuit in which a high-dimensional encoding of stimulus identity is collapsed onto a low-dimensional encoding of motivational valence.
PubMed: 37577586
DOI: 10.1101/2023.08.01.551547 -
Current Biology : CB Apr 2021Pleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics,...
Pleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics, we report here that stimulating the representation of pleasant odorants in a sensory structure, the pOB, can be rewarding, self-motivating, and is accompanied by ventral tegmental area activation. To explore the underlying neural circuitry downstream of the olfactory bulb (OB), we use 3D high-resolution imaging and optogenetics and determine that the pOB preferentially projects to the olfactory tubercle, whose increased activity is related to odorant attraction. We further show that attractive odorants act as reinforcers in dopamine-dependent place preference learning. Finally, we extend those findings to humans, who exhibit place preference learning and an increase BOLD signal in the olfactory tubercle in response to attractive odorants. Thus, strong and persistent attraction induced by some odorants is due to a direct gateway from the pOB to the reward system.
Topics: Animals; Emotions; Male; Mice; Mice, Inbred C57BL; Motivation; Odorants; Olfactory Bulb; Olfactory Perception; Optogenetics; Reward; Smell
PubMed: 33607032
DOI: 10.1016/j.cub.2021.01.066 -
CNS Neuroscience & Therapeutics Mar 2023This study aimed to explore the neural substrate of hearing loss-related central nervous system in rats and its correlation with cognition.
AIMS
This study aimed to explore the neural substrate of hearing loss-related central nervous system in rats and its correlation with cognition.
METHODS
We identified the neural mechanism for these debilitating abnormalities by inducing a bilateral hearing loss animal model using intense broadband noise (122 dB of broadband noise for 2 h) and used the Morris water maze test to characterize the behavioral changes at 6 months post-noise exposure. Functional magnetic resonance imaging (fMRI) was conducted to clarify disrupted functional network using bilateral auditory cortex (ACx) as a seed. Structural diffusion tensor imaging (DTI) was applied to illustrate characteristics of fibers in ACx and hippocampus. Pearson correlation was computed behavioral tests and other features.
RESULTS
A deficit in spatial learning/memory, body weight, and negative correlation between them was observed. Functional connectivity revealed weakened coupling within the ACx and inferior colliculus, lateral lemniscus, the primary motor cortex, the olfactory tubercle, hippocampus, and the paraflocculus lobe of the cerebellum. The fiber number and mean length of ACx and different hippocampal subregions were also damaged in hearing loss rats.
CONCLUSION
A new model of auditory-limbic-cerebellum interactions accounting for noise-induced hearing loss and cognitive impairments is proposed.
Topics: Rats; Animals; Hearing Loss, Noise-Induced; Diffusion Tensor Imaging; Auditory Pathways; Cognitive Dysfunction; Cerebellum
PubMed: 36377461
DOI: 10.1111/cns.14028 -
Proceedings of the National Academy of... Mar 2020The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district...
The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district regulates the limbic function of motivation, reward, and emotion. The dorsoventral parcellation of the striatum also is of clinical importance as differential striatal pathophysiologies occur in Huntington's disease, Parkinson's disease, and drug addiction disorders. Despite these striking neurobiologic contrasts, it is largely unknown how the dorsal and ventral divisions of the striatum are set up. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and the ventral striata including the D1-direct and D2-indirect pathways. We show that Nolz-1, through the I12b enhancer, represses , allowing normal migration of striatal neurons to dorsal and ventral locations. We demonstrate that deletion, up-regulation, and down-regulation of and can produce a striatal phenotype characterized by a withered dorsal striatum and an enlarged ventral striatum and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. Our study indicates that the two-tier system of striatal complex is built by coupling of cell-type identity and migration and suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into developing striata.
Topics: Animals; Basal Ganglia; Cell Differentiation; Corpus Striatum; Female; Homeodomain Proteins; Interneurons; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Nucleus Accumbens; Transcription Factors; Ventral Striatum
PubMed: 32170006
DOI: 10.1073/pnas.1921007117 -
International Journal of Molecular... May 2021is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine... (Review)
Review
is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. is expressed at high levels in the dorsal striatum, with a medial-to-lateral expression gradient reflecting that of both dopamine D and adenosine A receptors. transcript is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with -dependent regulation of dopaminergic transmission, data showed that lack of enhanced cocaine- and amphetamine-induced motor stimulation in mice. Previous studies showed that pharmacological depletion of dopamine significantly reduces mRNA levels in rodents, non-human primates and Parkinson's disease (PD) patients, suggesting a link between dopaminergic innervation and physiological mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L-DOPA-induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes-dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system.
Topics: Animals; Autophagy; Brain; Corpus Striatum; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dopaminergic Neurons; GTP-Binding Proteins; Gene Expression Regulation; Humans; Levodopa; Mice; Mice, Knockout; Mitophagy; Models, Neurological; Nerve Degeneration; Parkinson Disease; Parkinsonian Disorders; RNA, Messenger; Signal Transduction; Synaptic Transmission
PubMed: 34070217
DOI: 10.3390/ijms22105326 -
The Journal of Comparative Neurology Oct 2022The current study provides a detailed architectural analysis of the subpallial telencephalon of the tree pangolin. In the tree pangolin, the subpallial telencephalon was...
The current study provides a detailed architectural analysis of the subpallial telencephalon of the tree pangolin. In the tree pangolin, the subpallial telencephalon was divided into septal and striatopallidal regions. The septal region contained the septal nuclear complex, diagonal band of Broca, and the bed nuclei of the stria terminalis. The striatopallidal region comprised of the dorsal (caudate, putamen, internal and external globus pallidus) and ventral (nucleus accumbens, olfactory tubercle, ventral pallidum, nucleus basalis, basal part of the substantia innominata, lateral stripe of the striatum, navicular nucleus, and the major island of Calleja) striatopallidal complexes. In the tree pangolin, the organization and numbers of nuclei forming these regions and complexes, their topographical relationships to each other, and the cyto-, myelo-, and chemoarchitecture, were found to be very similar to that observed in commonly studied mammals. Minor variations, such as less nuclear parcellation in the bed nuclei of the stria terminalis, may represent species-specific variations, or may be the result of the limited range of stains used. Given the overall similarity across mammalian species, it appears that the subpallial telencephalon of the mammalian brain is highly conserved in terms of evolutionary changes detectable with the methods used. It is also likely that the functions associated with these nuclei in other mammals can be translated directly to the tree pangolin, albeit with the understanding that the stimuli that produce activity within these regions may be specific to the life history requirements of the tree pangolin.
Topics: Animals; Brain; Pangolins; Septum of Brain; Telencephalon
PubMed: 35708120
DOI: 10.1002/cne.25353