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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 -
Neurobiology of Aging May 2024Hedonic perception deeply changes with aging, significantly impacting health and quality of life in elderly. In young adult mice, an odor hedonic signature is...
Hedonic perception deeply changes with aging, significantly impacting health and quality of life in elderly. In young adult mice, an odor hedonic signature is represented along the antero-posterior axis of olfactory bulb, and transferred to the olfactory tubercle and ventral tegmental area, promoting approach behavior. Here, we show that while the perception of unattractive odorants was unchanged in older mice (22 months), the appreciation of some but not all attractive odorants declined. Neural activity in the olfactory bulb and tubercle of older mice was consistently altered when attraction to pleasant odorants was impaired while maintained when the odorants kept their attractivity. Finally, in a self-stimulation paradigm, optogenetic stimulation of the olfactory bulb remained rewarding in older mice even without ventral tegmental area's response to the stimulation. Aging degrades behavioral and neural responses to some pleasant odorants but rewarding properties of olfactory bulb stimulation persisted, providing new insights into developing novel olfactory training strategies to elicit motivation even when the dopaminergic system is altered as observed in normal and/or neurodegenerative aging.
Topics: Humans; Mice; Animals; Aged; Odorants; Smell; Olfactory Perception; Quality of Life; Olfactory Bulb
PubMed: 38394723
DOI: 10.1016/j.neurobiolaging.2024.02.003 -
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 -
Nature Communications Jun 2022Identifying the circuits responsible for cognition and understanding their embedded computations is a challenge for neuroscience. We establish here a hierarchical...
Identifying the circuits responsible for cognition and understanding their embedded computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach, from behavioral modeling and fMRI in task-performing mice to cellular recordings, in order to disentangle local network contributions to olfactory reinforcement learning. At mesoscale, fMRI identifies a functional olfactory-striatal network interacting dynamically with higher-order cortices. While primary olfactory cortices respectively contribute only some value components, the downstream olfactory tubercle of the ventral striatum expresses comprehensively reward prediction, its dynamic updating, and prediction error components. In the tubercle, recordings reveal two underlying neuronal populations with non-redundant reward prediction coding schemes. One population collectively produces stabilized predictions as distributed activity across neurons; in the other, neurons encode value individually and dynamically integrate the recent history of uncertain outcomes. These findings validate a cross-scale approach to mechanistic investigations of higher cognitive functions in rodents.
Topics: Animals; Cerebral Cortex; Magnetic Resonance Imaging; Mice; Olfactory Tubercle; Reinforcement, Psychology; Reward; Ventral Striatum
PubMed: 35676281
DOI: 10.1038/s41467-022-30978-1 -
Current Biology : CB Dec 2021Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and the principal interface between dopamine reward signals and functionally diverse...
Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and the principal interface between dopamine reward signals and functionally diverse cortico-basal ganglia circuits. Information processing in these circuits is dependent on distinct MSN types: cell types that are traditionally defined according to their projection targets or dopamine receptor expression. Single-cell transcriptional studies have revealed greater MSN heterogeneity than predicted by traditional circuit models, but the transcriptional landscape in the primate striatum remains unknown. Here, we set out to establish molecular definitions for MSN subtypes in Rhesus monkeys and to explore the relationships between transcriptionally defined subtypes and anatomical subdivisions of the striatum. Our results suggest at least nine MSN subtypes, including dorsal striatum subtypes associated with striosome and matrix compartments, ventral striatum subtypes associated with the nucleus accumbens shell and olfactory tubercle, and an MSN-like cell type restricted to μ-opioid receptor rich islands in the ventral striatum. Although each subtype was demarcated by discontinuities in gene expression, continuous variation within subtypes defined gradients corresponding to anatomical locations and, potentially, functional specializations. These results lay the foundation for achieving cell-type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit-specific information processing.
Topics: Animals; Corpus Striatum; Dopamine; Mice; Mice, Inbred C57BL; Neostriatum; Neurons; Primates
PubMed: 34727523
DOI: 10.1016/j.cub.2021.10.015 -
Cerebral Cortex (New York, N.Y. : 1991) Oct 2020The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better...
The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better its roles in emotion and its disorders. The medial OFC and ventromedial prefrontal cortex have direct connections with the pregenual and subgenual parts of the anterior cingulate cortex; all of which are reward-related areas. The lateral OFC (OFClat) and its closely connected right inferior frontal gyrus (rIFG) have direct connections with the supracallosal anterior cingulate cortex; all of which are punishment or nonreward-related areas. The OFClat and rIFG also have direct connections with the right supramarginal gyrus and inferior parietal cortex, and with some premotor cortical areas, which may provide outputs for the OFClat and rIFG. Another key finding is that the ventromedial prefrontal cortex shares with the medial OFC especially strong outputs to the nucleus accumbens and olfactory tubercle, which comprise the ventral striatum, whereas the other regions have more widespread outputs to the striatum. Direct connections of the OFC and IFG were with especially the temporal pole part of the temporal lobe. The left IFG, which includes Broca's area, has direct connections with the left angular and supramarginal gyri.
Topics: Adult; Aged; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Neural Pathways; Prefrontal Cortex
PubMed: 32548630
DOI: 10.1093/cercor/bhaa160 -
Medicine and Science in Sports and... Aug 2018Exercise has been shown to be effective for preventing and treating substance abuse in both clinical and preclinical studies. Less is known, however, regarding the...
INTRODUCTION
Exercise has been shown to be effective for preventing and treating substance abuse in both clinical and preclinical studies. Less is known, however, regarding the underlying neurobiological mechanisms driving these changes in drug-seeking behavior. One possibility is that exercise may alter the mesolimbic dopamine pathway in such a way that makes drugs of abuse less salient and/or rewarding.
METHODS
To examine possible exercise-induced changes in dopamine signaling, male and female Lewis rats were split into exercise and sedentary groups at 8 wk of age. Exercise rats were run on a treadmill at 10 m·min, 5 d·wk, for 6 wk, whereas sedentary rats remained in their home cage. Rats were killed after the 6 wk of treatment, and their brains were used for in vitro autoradiography using [H]SCH 23,390, [H]Spiperone, and [H]WIN55,428 ligands to quantify dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and dopamine transporter binding, respectively.
RESULTS
Exercised rats had 18% and 21% lower D1R-like binding levels compared to sedentary rats within the olfactory tubercle and nucleus accumbens shell, respectively. In addition, male and female exercise rats showed greater D2R-like binding levels within the dorsomedial caudate putamen (30%), ventrolateral caudate putamen (24%), and ventromedial caudate putamen (27%), as well as the olfactory tubercle (19%). Greater D2R-like binding in the nucleus accumbens core (24%) and shell (25%) of exercised rats compared with sedentary rats approached significance. No effects were found for dopamine transporter binding.
CONCLUSIONS
These findings support the hypothesis that aerobic exercise results in changes in the mesolimbic pathway that could mediate exercise-induced attenuation of drug-seeking behavior.
Topics: Animals; Autoradiography; Brain; Cocaine-Related Disorders; Exercise Therapy; Female; Male; Nucleus Accumbens; Olfactory Tubercle; Physical Conditioning, Animal; Putamen; Rats, Inbred Lew; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 29613999
DOI: 10.1249/MSS.0000000000001627 -
Brain Research Dec 2014Animals maintained under conditions of food-availability restricted to a specific period of the day show molecular and physiological circadian rhythms and increase their...
Animals maintained under conditions of food-availability restricted to a specific period of the day show molecular and physiological circadian rhythms and increase their locomotor activity 2-3h prior to the next scheduled feeding, called food anticipatory activity (FAA). Although the anatomical substrates and underlying mechanisms of the food-entrainable oscillator are not well understood, experimental evidence indicates that it involves multiple structures and systems. Using rabbit pups entrained to circadian nursing as a natural model of food restriction, we hypothesized that the anterior piriform cortex (APCx) and the olfactory tubercle (OTu) are activated during nursing-associated FAA. Two groups of litters were entrained to one of two different nursing times. At postnatal day 7, when litters showed clear FAA, pups from each litter were euthanized at nursing time, or 1, 2, 4, 8, 12, 16 or 20h later. Neural metabolic activities of the APCx, OTu, olfactory bulb (OB) and suprachiasmatic nucleus (SCN) were assessed by cytochrome oxidase histochemistry. Additionally, two fasted groups were nurse-deprived for two cycles before being euthanized at postnatal day 9. In nursed pups, metabolic activity of APCx, OTu and OB increased during FAA and after feeding, independently of the geographical time. Metabolic activity in SCN was not affected by nursing schedule. Given that APCx and OTu are in a key network position to integrate temporal odor signals with body energetic state, brain arousal and reward mechanisms, we suggest that these structures could be an important part of the conditioned oscillatory mechanism that leads to food entrainment.
Topics: Animals; Animals, Newborn; Anticipation, Psychological; Circadian Rhythm; Electron Transport Complex IV; Feeding Behavior; Food Deprivation; Lactation; Motor Activity; Olfactory Bulb; Olfactory Tubercle; Piriform Cortex; Rabbits; Random Allocation; Suprachiasmatic Nucleus
PubMed: 25281805
DOI: 10.1016/j.brainres.2014.09.054 -
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