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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 -
Journal of Alzheimer's Disease : JAD 2019The nucleus basalis of Meynert (nbM) was first described at the end of the 19th century and named after its discoverer, Theodor Meynert. The nbM contains a large... (Review)
Review
The nucleus basalis of Meynert (nbM) was first described at the end of the 19th century and named after its discoverer, Theodor Meynert. The nbM contains a large population of cholinergic neurons that project their axons to the entire cortical mantle, the olfactory tubercle, and the amygdala. It has been functionally associated with the control of attention and maintenance of arousal, both key functions for appropriate learning and memory formation. This structure is well-conserved across vertebrates, although its degree of organization varies between species. Since early in the investigation of its functional and pathological significance, its degeneration has been linked to various major neuropsychiatric disorders. For instance, Lewy bodies, a hallmark in the diagnosis of Parkinson's disease, were originally described in the nbM. Since then, its involvement in other Lewy body and dementia-related disorders has been recognized. In the context of recent positive outcomes following nbM deep brain stimulation in subjects with dementia-associated disorders, we review the literature from an historical perspective focusing on how the nbM came into focus as a promising therapeutic option for patients with Alzheimer's disease. Moreover, we will discuss what is needed to further develop and widely implement this approach as well as examine novel medical indications for which nbM deep brain stimulation may prove beneficial.
Topics: Alzheimer Disease; Basal Nucleus of Meynert; Cognition Disorders; Deep Brain Stimulation; History, 19th Century; History, 20th Century; History, 21st Century; Humans
PubMed: 31104014
DOI: 10.3233/JAD-180133 -
Scientific Reports May 2019Olfaction guides goal-directed behaviours including feeding. To investigate how central olfactory neural circuits control feeding behaviour in mice, we performed...
Olfaction guides goal-directed behaviours including feeding. To investigate how central olfactory neural circuits control feeding behaviour in mice, we performed retrograde tracing from the lateral hypothalamus (LH), an important feeding centre. We observed a cluster of retrogradely labelled cells distributed in the posteroventral region of the olfactory peduncle. Histochemical analyses revealed that the majority of these retrogradely labelled projection neurons expressed glutamic acid decarboxylase 65/67 (GAD65/67), but not vesicular glutamate transporter 1 (VGluT1). We named this region containing GABAergic projection neurons the ventral olfactory nucleus (VON) to differentiate it from the conventional olfactory peduncle. VON neurons were less immunoreactive for DARPP-32, a striatal neuron marker, compared to neurons in the olfactory tubercle and nucleus accumbens, which distinguished the VON from the ventral striatum. Fluorescent labelling confirmed putative synaptic contacts between VON neurons and olfactory bulb projection neurons. Rabies-virus-mediated trans-synaptic labelling revealed that VON neurons received synaptic inputs from the olfactory bulb, other olfactory cortices, horizontal limb of the diagonal band, and prefrontal cortex. Collectively, these results identify novel GABAergic projection neurons in the olfactory cortex that may integrate olfactory sensory and top-down inputs and send inhibitory output to the LH, which may modulate odour-guided LH-related behaviours.
Topics: Animals; Feeding Behavior; GABAergic Neurons; Glutamate Decarboxylase; Hypothalamic Area, Lateral; Male; Mice; Olfactory Bulb; Olfactory Cortex; Rabies virus; Vesicular Glutamate Transport Protein 1
PubMed: 31073137
DOI: 10.1038/s41598-019-43580-1 -
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 -
Brain Research Bulletin Oct 2016It was revealed that regeneration of the lateral olfactory tract (LOT) occurred in developing rats and the regenerated olfactory system was functional 4 weeks after...
It was revealed that regeneration of the lateral olfactory tract (LOT) occurred in developing rats and the regenerated olfactory system was functional 4 weeks after transection. The aim of this study was to determine the earliest onset of functional recovery in LOT-injured rats and to quantify regenerated nerve components with functional correlation. Neonatal rats on postnatal day (P) 2 were subjected to unilateral transection of the left LOT and underwent unilateral removal of the right olfactory bulb on P11. Functional recovery of the tract injury was assessed by the suckling capability, which can be achieved by olfaction. Suckling capability was observed on P12 in most neonatally LOT-transected pups. Rat pups were subjected to unilateral transection of the left LOT on P2, and received injections of biotinylated dextran amine (BDA) into the bilateral olfactory bulb on P5 to quantify normal and regenerated nerve components in the olfactory cortices at the level of the olfactory tubercle. BDA(+) areas and density indices of the olfactory cortices in the neonatally LOT-transected P12 pups were 11.05×10μm and 0.35 on the normal right side and 4.34×10μm and 0.21 on the transected left side. We concluded that functional recovery of the LOT-transected neonatal rats occurred as early as 10days after tract transection and that areas and densities of regenerated nerve components essential for functional recovery were approximately 40% and 60% of the age-matched normal values in the olfactory cortices at the level of the olfactory tubercle.
Topics: Animals; Animals, Newborn; Biotin; Dextrans; Fluorescent Dyes; Nerve Regeneration; Neuronal Tract-Tracers; Olfactory Bulb; Olfactory Cortex; Olfactory Pathways; Rats, Wistar; Recovery of Function; Smell; Sucking Behavior
PubMed: 27575005
DOI: 10.1016/j.brainresbull.2016.08.015 -
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 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 -
Frontiers in Molecular Neuroscience 2020Trace amine-associated receptors (TAARs) are a class of G-protein-coupled receptors found in mammals. While TAAR1 is expressed in several brain regions, all the other...
Trace amine-associated receptors (TAARs) are a class of G-protein-coupled receptors found in mammals. While TAAR1 is expressed in several brain regions, all the other TAARs have been described mainly in the olfactory epithelium and the glomerular layer of the olfactory bulb and are believed to serve as a new class of olfactory receptors sensing innate odors. However, there is evidence that TAAR5 could play a role also in the central nervous system. In this study, we characterized a mouse line lacking TAAR5 (TAAR5 knockout, TAAR5-KO) expressing beta-galactosidase mapping TAAR5 expression. We found that TAAR5 is expressed not only in the glomerular layer in the olfactory bulb but also in deeper layers projecting to the limbic brain olfactory circuitry with prominent expression in numerous limbic brain regions, such as the anterior olfactory nucleus, the olfactory tubercle, the orbitofrontal cortex (OFC), the amygdala, the hippocampus, the piriform cortex, the entorhinal cortex, the nucleus accumbens, and the thalamic and hypothalamic nuclei. TAAR5-KO mice did not show gross developmental abnormalities but demonstrated less anxiety- and depressive-like behavior in several behavioral tests. TAAR5-KO mice also showed significant decreases in the tissue levels of serotonin and its metabolite in several brain areas and were more sensitive to the hypothermic action of serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di--propilamino)tetralin (8-OH-DPAT). These observations indicate that TAAR5 is not just innate odor-sensing olfactory receptor but also serves to provide olfactory input into limbic brain areas to regulate emotional behaviors likely modulation of the serotonin system. Thus, anxiolytic and/or antidepressant action of future TAAR5 antagonists could be predicted. In general, "olfactory" TAAR-mediated brain circuitry may represent a previously unappreciated neurotransmitter system involved in the transmission of innate odors into emotional behavioral responses.
PubMed: 32194374
DOI: 10.3389/fnmol.2020.00018 -
Frontiers in Neuroanatomy 2016The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA),...
The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors related to reproductive or defensive behaviors.
PubMed: 28066196
DOI: 10.3389/fnana.2016.00125