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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 -
Neuroscience and Biobehavioral Reviews Nov 2010Reductionist attempts to dissect complex mechanisms into simpler elements are necessary, but not sufficient for understanding how biological properties like reward... (Review)
Review
Reductionist attempts to dissect complex mechanisms into simpler elements are necessary, but not sufficient for understanding how biological properties like reward emerge out of neuronal activity. Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures-the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle. In addition, studies found roles of non-dopaminergic mechanisms of the supramammillary, rostromedial tegmental and midbrain raphe nuclei in reward. To explain intracranial self-administration and related effects of various drug manipulations, I outlined a neurobiological theory claiming that there is an intrinsic central process that coordinates various selective functions (including perceptual, visceral, and reinforcement processes) into a global function of approach. Further, this coordinating process for approach arises from interactions between brain structures including those structures mentioned above and their closely linked regions: the medial prefrontal cortex, septal area, ventral pallidum, bed nucleus of stria terminalis, preoptic area, lateral hypothalamic areas, lateral habenula, periaqueductal gray, laterodorsal tegmental nucleus and parabrachical area.
Topics: Animals; Brain; Dopamine; Models, Neurological; Neural Pathways; Reward; Self Administration
PubMed: 20149820
DOI: 10.1016/j.neubiorev.2010.02.001 -
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 -
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 -
The Journal of Neuroscience : the... Nov 2019Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary"...
Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary" olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Further unresolved is the synaptic circuitry and the spatial localization of OT-innervating PCX neurons. Here we build upon standing literature to provide some answers to these questions through studies in mice of both sexes. First, we recorded the activity of OT neurons in awake mice while optically stimulating principal neurons in the aPCX and/or their association fibers in the OT while the mice were delivered odors. This uncovered evidence that PCX input indeed influences OT unit activity. We then used patch-clamp recordings and viral tracing to determine the connectivity of aPCX neurons upon OT neurons expressing dopamine receptor types D1 or D2, two prominent cell populations in the OT. These investigations uncovered that both populations of neurons receive monosynaptic inputs from aPCX glutamatergic neurons. Interestingly, this input originates largely from the ventrocaudal aPCX. These results shed light on some of the basic physiological properties of this pathway and the cell-types involved and provide a foundation for future studies to identify, among other things, whether this pathway has implications for perception. Sensory cortices interact to process stimuli in manners considered essential for perception. Very little is known regarding interactions between olfactory cortices. The present study sheds light on some of the basic physiological properties of a particular intercortical pathway in the olfactory system and provides a foundation for future studies to identify, among other things, whether this pathway has implications for perception.
Topics: Animals; Female; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Odorants; Olfactory Receptor Neurons; Olfactory Tubercle; Piriform Cortex; Receptors, Dopamine D1; Receptors, Dopamine D2; Smell
PubMed: 31628176
DOI: 10.1523/JNEUROSCI.1444-19.2019 -
ELife Dec 2017Odor-preferences are usually influenced by life experiences. However, the neural circuit mechanisms remain unclear. The medial olfactory tubercle (mOT) is involved in...
Odor-preferences are usually influenced by life experiences. However, the neural circuit mechanisms remain unclear. The medial olfactory tubercle (mOT) is involved in both reward and olfaction, whereas the ventral tegmental area (VTA) dopaminergic (DAergic) neurons are considered to be engaged in reward and motivation. Here, we found that the VTA (DAergic)-mOT pathway could be activated by different types of naturalistic rewards as well as odors in DAT-cre mice. Optogenetic activation of the VTA-mOT DAergic fibers was able to elicit preferences for space, location and neutral odor, while pharmacological blockade of the dopamine receptors in the mOT fully prevented the odor-preference formation. Furthermore, inactivation of the mOT-projecting VTA DAergic neurons eliminated the previously formed odor-preference and strongly affected the Go-no go learning efficiency. In summary, our results revealed that the VTA (DAergic)-mOT pathway mediates a variety of naturalistic reward processes and different types of preferences including odor-preference in mice.
Topics: Animals; Behavior, Animal; Dopaminergic Neurons; Mice; Neural Pathways; Odorants; Olfactory Tubercle; Optogenetics; Ventral Tegmental Area
PubMed: 29251597
DOI: 10.7554/eLife.25423 -
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 -
Life Sciences 1997By comparison to the other subtypes of muscarinic receptors, very little is known about the binding properties, locations, mechanisms and physiological functions of the... (Review)
Review
By comparison to the other subtypes of muscarinic receptors, very little is known about the binding properties, locations, mechanisms and physiological functions of the M5 (m5)* receptor subtype. Studies of the m5 receptor have been hampered by the lack of m5-selective ligands or antibodies and a source that endogenously expresses predominantly the m5 receptor subtype. We have developed a pharmacological labeling strategy using the non-selective muscarinic antagonist [3H]NMS, in the presence of muscarinic antagonists and toxins in green mamba venom to occlude the m1-m4 receptor subtypes, to selectively label the m5 receptor subtype. This m5-selective labeling approach, along with those developed for the other four receptor subtypes, has permitted for the first time a comparison of the relative expression levels and anatomical localizations of the five muscarinic receptor subtypes in the brain. The distribution profile of the m5 receptor is distinct from the other four subtypes and is enriched in the outer layers of the cortex, specific subfields of the hippocampus, caudate putamen, olfactory tubercle and nucleus accumbens. These studies have also demonstrated that the levels of m5 receptor protein expression are apparently higher and more widespread than anticipated from previous in situ hybridization and immunoprecipitation studies. Taken together, the results suggest a unique and potentially physiologically important role for the m5 receptor subtype in modulating the actions of acetylcholine in the brain.
Topics: Animals; Brain Chemistry; Humans; Receptors, Muscarinic
PubMed: 9121354
DOI: 10.1016/s0024-3205(97)00054-4