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Nature Neuroscience Nov 2021The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally...
The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally opposing information and participates in establishing valence-specific behaviors remains unclear. Here, by targeting Fezf2-expressing neurons in the BLA, we identify and characterize two functionally distinct classes in behaving mice, the negative-valence neurons and positive-valence neurons, which innately represent aversive and rewarding stimuli, respectively, and through learning acquire predictive responses that are essential for punishment avoidance or reward seeking. Notably, these two classes of neurons receive inputs from separate sets of sensory and limbic areas, and convey punishment and reward information through projections to the nucleus accumbens and olfactory tubercle, respectively, to drive negative and positive reinforcement. Thus, valence-specific BLA neurons are wired with distinctive input-output structures, forming a circuit framework that supports the roles of the BLA in encoding, learning and executing valence-specific motivated behaviors.
Topics: Amygdala; Animals; Attention; Avoidance Learning; Corpus Striatum; DNA-Binding Proteins; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motivation; Nerve Net; Nerve Tissue Proteins
PubMed: 34663958
DOI: 10.1038/s41593-021-00927-0 -
The Journal of Comparative Neurology May 2022Corticothalamic interactions between associative cortices and higher order thalamic nuclei are involved in high-cognitive functions such as decision-making and working...
Corticothalamic interactions between associative cortices and higher order thalamic nuclei are involved in high-cognitive functions such as decision-making and working memory. Corticothalamic neurons (CTn) in the prefrontal cortex and other associative areas have been much less studied than their counterparts in the primary sensory areas. The availability of characterized transgenic tools to study CTn in associative areas will facilitate their study and contribute to overcome the scarcity of data about their properties, network dynamics, and contribution to cognitive functions. Here, we characterized the Syt6-Cre (KI148Gsat/Mmud) transgenic mouse line, by tracking expression of a Cre-mediated reporter. In this line, Cre-reporter is strongly expressed in the prefrontal, motor, cingulate, and retrosplenial cortices, as well as in other brain areas including the cerebellum and the olfactory tubercle. Cortical expression starts embryonically and reaches the adult expression pattern by postnatal day 15. In the cortex, Cre-reporter is expressed by layer 6-CTn and by layer 5-CTn to a lesser extent. We quantified Syt6-Cre CTn axon varicosities to estimate the distribution and density of putative corticothalamic driver and modulator inputs to thalamic nuclei in the medial, midline, intralaminar, anterior, and motor groups. Also, we characterized the effect of optogenetic stimulation of Syt6-Cre neurons in the activity of the prefrontal cortex. CTn stimulation in the prefrontal cortex induces an oscillatory activity in the local field potential that resembles the cortical downstates typically observed during slow-wave sleep or quiet wake.
Topics: Animals; Cerebral Cortex; Integrases; Mice; Mice, Transgenic; Neural Pathways; Neurons
PubMed: 34617601
DOI: 10.1002/cne.25256 -
Foods (Basel, Switzerland) Aug 2021The anterior insula and rolandic operculum are key regions for flavour perception in the human brain; however, it is unclear how taste and congruent retronasal smell are...
The anterior insula and rolandic operculum are key regions for flavour perception in the human brain; however, it is unclear how taste and congruent retronasal smell are perceived as flavours. The multisensory integration required for sour flavour perception has rarely been studied; therefore, we investigated the brain responses to taste and smell in the sour flavour-processing network in 35 young healthy adults. We aimed to characterise the brain response to three stimulations applied in the oral cavity-sour taste, retronasal smell of mango, and combined flavour of both-using functional magnetic resonance imaging. Effective connectivity of the flavour-processing network and modulatory effect from taste and smell were analysed. Flavour stimulation activated middle insula and olfactory tubercle (primary taste and olfactory cortices, respectively); anterior insula and rolandic operculum, which are associated with multisensory integration; and ventrolateral prefrontal cortex, a secondary cortex for flavour perception. Dynamic causal modelling demonstrated that neural taste and smell signals were integrated at anterior insula and rolandic operculum. These findings elucidated how neural signals triggered by sour taste and smell presented in liquid form interact in the brain, which may underpin the neurobiology of food appreciation. Our study thus demonstrated the integration and synergy of taste and smell.
PubMed: 34574144
DOI: 10.3390/foods10092034 -
International Journal of Molecular... Aug 2021Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible posttranslational modifications of proteins and their enzymatic activities contribute to the...
Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible posttranslational modifications of proteins and their enzymatic activities contribute to the pathogenesis of several human neurodegenerative diseases. Although different transglutaminases are found in many different tissues, the TG6 isoform is mostly expressed in the CNS. The present study was embarked on/undertaken to investigate expression, distribution and activity of transglutaminases in Huntington disease transgenic rodent models, with a focus on analyzing the involvement of TG6 in the age- and genotype-specific pathological features relating to disease progression in HD transgenic mice and a tgHD transgenic rat model using biochemical, histological and functional assays. Our results demonstrate the physical interaction between TG6 and (mutant) huntingtin by co-immunoprecipitation analysis and the contribution of its enzymatic activity for the total aggregate load in SH-SY5Y cells. In addition, we identify that TG6 expression and activity are especially abundant in the olfactory tubercle and piriform cortex, the regions displaying the highest amount of mHTT aggregates in transgenic rodent models of HD. Furthermore, mHTT aggregates were colocalized within TG6-positive cells. These findings point towards a role of TG6 in disease pathogenesis via mHTT aggregate formation.
Topics: Animals; Disease Models, Animal; Huntingtin Protein; Huntington Disease; Mice; Mice, Transgenic; Mutant Proteins; Mutation; Neurons; Rats; Transglutaminases
PubMed: 34445621
DOI: 10.3390/ijms22168914 -
Brain Research Oct 2021Depression, rapid eye movement (REM) sleep behavior disorder, and altered olfaction are often present in Parkinson's disease. Our previous studies demonstrated the role...
Depression, rapid eye movement (REM) sleep behavior disorder, and altered olfaction are often present in Parkinson's disease. Our previous studies demonstrated the role of the olfactory bulb (OB) in causing REM sleep disturbances in depression. Furthermore, adenosine A receptors (AR) which are richly expressed in the OB, play an important role in the regulation of REM sleep. Caffeine, an adenosine A receptors and AR antagonist, and other AR antagonists were reported to improve olfactory function and restore age-related olfactory deficits. Therefore, we hypothesized that the AR neurons in the OB may regulate olfaction or odor-guided behaviors in mice. In the present study, we employed chemogenetics to specifically activate or inhibit neuronal activity. Then, buried food test and olfactory habituation/dishabituation test were performed to measure the changes in the mice's olfactory ability. We demonstrated that activation of OB neurons or OB AR neurons shortened the latency of buried food test and enhanced olfactory habituation to the same odors and dishabituation to different odors; inhibition of these neurons showed the opposite effects. Photostimulation of ChR2-expressing OB AR neuron terminals evoked inward current in the olfactory tubercle (OT) and the piriform cortex (Pir), which was blocked by glutamate receptor antagonists 2-amino-5-phosphonopentanoic acid and 6-cyano-7nitroquinoxaline-2,3-dione. Collectively, these results suggest that the OB mediates olfaction via AR neurons in mice. Moreover, the excitatory glutamatergic release from OB neurons to the OT and the Pir were found responsible for the olfaction-mediated effects of OB AR neurons.
Topics: Animals; Male; Mice; Mice, Inbred C57BL; Neurons; Odorants; Olfactory Bulb; Olfactory Cortex; Olfactory Perception; Piriform Cortex; Receptor, Adenosine A2A; Smell
PubMed: 34310936
DOI: 10.1016/j.brainres.2021.147590 -
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 -
Frontiers in Neuroanatomy 2021The uptake, transmission and processing of sensory olfactory information is modulated by inhibitory and excitatory receptors in the olfactory system. Previous studies...
The uptake, transmission and processing of sensory olfactory information is modulated by inhibitory and excitatory receptors in the olfactory system. Previous studies have focused on the function of individual receptors in distinct brain areas, but the receptor architecture of the whole system remains unclear. Here, we analyzed the receptor profiles of the whole olfactory system of adult male mice. We examined the distribution patterns of glutamatergic (AMPA, kainate, mGlu, and NMDA), GABAergic (GABA, GABA, and GABA), dopaminergic (D) and noradrenergic (α and α) neurotransmitter receptors by quantitative receptor autoradiography combined with an analysis of the cyto- and myelo-architecture. We observed that each subarea of the olfactory system is characterized by individual densities of distinct neurotransmitter receptor types, leading to a region- and layer-specific receptor profile. Thereby, the investigated receptors in the respective areas and strata showed a heterogeneous expression. Generally, we detected high densities of mGluRs, GABARs and GABARs. Noradrenergic receptors revealed a highly heterogenic distribution, while the dopaminergic receptor D displayed low concentrations, except in the olfactory tubercle and the dorsal endopiriform nucleus. The similarities and dissimilarities of the area-specific multireceptor profiles were analyzed by a hierarchical cluster analysis. A three-cluster solution was found that divided the areas into the (1) olfactory relay stations (main and accessory olfactory bulb), (2) the olfactory cortex (anterior olfactory cortex, dorsal peduncular cortex, taenia tecta, piriform cortex, endopiriform nucleus, entorhinal cortex, orbitofrontal cortex) and the (3) olfactory tubercle, constituting its own cluster. The multimodal receptor-architectonic analysis of each component of the olfactory system provides new insights into its neurochemical organization and future possibilities for pharmaceutic targeting.
PubMed: 33967704
DOI: 10.3389/fnana.2021.632549 -
Biology Letters Apr 2021Developmental studies of brain volumes can reveal which portions of neural circuits are sensitive to environmental inputs. In social insects, differences in relative...
Developmental studies of brain volumes can reveal which portions of neural circuits are sensitive to environmental inputs. In social insects, differences in relative investment across brain regions emerge as behavioural repertoires change during ontogeny or as a result of experience. Here, we test the effects of maturation and social experience on morphological brain development in paper wasps focusing on brain regions involved in visual and olfactory processing. We find that mature wasps regardless of social experience have relatively larger brains than newly emerged wasps and this difference is driven by changes to mushroom body calyx and visual regions but not olfactory processing neuropils. Notably, social wasps invest more in the anterior optic tubercle (AOT), a visual glomerulus involved in colour and object processing in other taxa, relative to other visual integration centres the mushroom body calyces compared with aged socially naive wasps. Differences in developmental plasticity between visual and olfactory neuropil volumes are discussed in light of behavioural maturation in paper wasps, especially as it relates to social recognition. Previous research has shown that need social experience to develop specialized visual processing of faces, which is used to individually recognize conspecifics. The present study suggests that the AOT is a candidate brain region that could mediate facial processing in this species.
Topics: Animals; Brain; Cognition; Recognition, Psychology; Wasps
PubMed: 33849349
DOI: 10.1098/rsbl.2021.0073 -
Neurochemical Research Jun 2021Activation of dopamine (DA) neurons is essential for the transition from sleep to wakefulness and maintenance of awakening, and sufficient to accelerate the emergence...
Activation of dopamine (DA) neurons is essential for the transition from sleep to wakefulness and maintenance of awakening, and sufficient to accelerate the emergence from general anesthesia in animals. Dopamine receptors (DR) are involve in arousal mediation. In the present study, we showed that the olfactory tubercle (OT) was active during emergence from isoflurane anesthesia, local injection of dopamine D1 receptor (D1R) agonist chloro-APB (1 mg/mL) and D2 receptor (D2R) agonist quinpirole (1 mg/mL) into OT enhanced behavioural and cortical arousal from isoflurane anesthesia, while D1R antagonist SCH-23390 (1 mg/mL) and D2R antagonist raclopride (2.5 mg/mL) prolonged recovery time. Optogenetic activation of DAergic terminals in OT also promoted behavioural and cortical arousal from isoflurane anesthesia. However, neither D1R/D2R agonists nor D1R/D2R antagonists microinjection had influences on the induction of isoflurane anesthesia. Optogenetic stimulation on DAergic terminals in OT also had no impact on the anesthesia induction. Our results indicated that DA signals in OT accelerated emergence from isoflurane anesthesia. Furthermore, the induction of general anesthesia, different from the emergence process, was not mediated by the OT DAergic pathways.
Topics: Anesthetics, Inhalation; Animals; Arousal; Benzazepines; Dopamine Agonists; Dopamine D2 Receptor Antagonists; Isoflurane; Male; Mice, Inbred C57BL; Olfactory Tubercle; Quinpirole; Raclopride; Receptors, Dopamine D1; Receptors, Dopamine D2; Mice
PubMed: 33710536
DOI: 10.1007/s11064-021-03291-4 -
The Journal of Nutrition May 2021A low-protein diet can induce compensatory intake of excess energy. This must be better evaluated to anticipate the obesogenic risk that may result from the dietary...
BACKGROUND
A low-protein diet can induce compensatory intake of excess energy. This must be better evaluated to anticipate the obesogenic risk that may result from the dietary recommendations for reducing animal protein consumption.
OBJECTIVES
We aimed to further characterize the behavioral and physiological responses to a reduction in dietary protein and to identify the determinants of protein appetite.
METHODS
Thirty-two male Wistar rats [4 wk old, (mean ± SEM) 135 ± 32 g body weight] were fed a low-protein (LP; 6% energy value) or normal-protein (NP; 20%) diet for 8 wk. Food intake and body mass were measured during the entire intervention. During self-selection sessions after 4 wk of experimental diets, we evaluated rat food preference between LP, NP, or high-protein (HP; 55%) pellets. At the end of the experiment, we assessed their hedonic response [ultrasonic vocalizations (USVs)] and c-Fos neuronal activation in the olfactory tubercle and nucleus accumbens (NAcc) associated with an LP or HP meal.
RESULTS
Rats fed an LP diet had greater food intake (24%), body weight (5%), and visceral adiposity (30%) than NP rats. All LP rats and half of the NP rats showed a nearly exclusive preference for HP pellets during self-selection sessions, whereas the other half of the NP rats showed no preference. This suggests that the appetite for proteins is driven not only by a low protein status but also by individual traits in NP rats. LP or HP meal induced similar USV emission and similar neuronal activation in the NAcc in feed-deprived LP and NP rats, showing no specific response linked to protein appetite.
CONCLUSIONS
Protein appetite in rats is driven by low protein status or individual preferences in rats receiving adequate protein amounts. This must be considered and further analyzed, in the context of current recommendations for protein intake reduction.
Topics: Adiposity; Animals; Appetite; Body Weight; Diet, Protein-Restricted; Dietary Proteins; Eating; Energy Intake; Food Preferences; Intra-Abdominal Fat; Male; Meat; Nucleus Accumbens; Obesity; Olfactory Tubercle; Phenotype; Rats, Wistar; Rats
PubMed: 33693927
DOI: 10.1093/jn/nxaa455