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Addiction Neuroscience Dec 2023Epidermal/brain fatty acid-binding protein 5 (FABP5) plays an integral role in the intracellular trafficking of bioactive lipids/endocannabinoids and the subsequent...
Epidermal/brain fatty acid-binding protein 5 (FABP5) plays an integral role in the intracellular trafficking of bioactive lipids/endocannabinoids and the subsequent initiation of cellular cascades affecting cannabinoid and dopamine (DA) systems. Social isolation (SI) and environmental enrichment (EE) during adolescence have been shown to impact DA signaling, and, specifically, DA transporter (DAT) and receptor levels of DA type 1 (D1) and 2 (D2); however, the relationship between FABP5, environment and DA signaling remains unclear. The present study quantified DAT and DA receptor levels in male/female FABP5-/- and FABP5+/+ mice raised in either SI or EE. Results showed that FABP5-/- mice had 6.09-8.81% greater D1 levels in striatal sub-regions of the caudal brain, independent of sex or environment. D1 levels were 8.03% greater only in the olfactory tubercle of enrichment-reared animals. In summary, these results supported that FABP5 plays an important function in regulating striatal DA signaling, and this may have important implications as a target with therapeutic potential for various psychiatric disorders.
PubMed: 37664218
DOI: 10.1016/j.addicn.2023.100118 -
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 -
Neural Regeneration Research Nov 2023Sleep benefits the restoration of energy metabolism and thereby supports neuronal plasticity and cognitive behaviors. Sirt6 is a NAD-dependent protein deacetylase that...
Sleep benefits the restoration of energy metabolism and thereby supports neuronal plasticity and cognitive behaviors. Sirt6 is a NAD-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes. The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation (CSD). We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex (PrL). We then assessed cerebral functional connectivity (FC) using resting-state functional MRI, neuron/astrocyte metabolism using a metabolic kinetics analysis; dendritic spine densities using sparse-labeling; and miniature excitatory postsynaptic currents (mEPSCs) and action potential (AP) firing rates using whole-cell patch-clamp recordings. In addition, we evaluated cognition via a comprehensive set of behavioral tests. Compared with controls, Sirt6 was significantly decreased (P < 0.05) in the PrL after CSD, accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus, piriform cortex, motor cortex, somatosensory cortex, olfactory tubercle, insular cortex, and cerebellum. Sirt6 overexpression reversed CSD-induced cognitive impairment and reduced FC. Our analysis of metabolic kinetics using [1-C] glucose and [2-C] acetate showed that CSD reduced neuronal Glu and GABA synthesis, which could be fully restored via forced Sirt6 expression. Furthermore, Sirt6 overexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons. These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network, neuronal glucose metabolism, and glutamatergic neurotransmission. Thus, Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.
PubMed: 37282476
DOI: 10.4103/1673-5374.371370 -
Synapse (New York, N.Y.) Jul 2023Olfaction is a complex physiological process producing effects in the central nervous system (CNS) and implicated in emotional processes. Indeed, the olfactory bulbs...
Olfaction is a complex physiological process producing effects in the central nervous system (CNS) and implicated in emotional processes. Indeed, the olfactory bulbs (OB) send projections to various CNS regions including the nucleus accumbens (NAcc) and caudate-putamen (CPu). Both the NAcc and CPu receive important dopaminergic input. Emerging evidence suggests that dopamine (DA) is related to anxiety-related behaviors. Therefore, we aimed to investigate the consequences of neonatal olfactory bulbectomy (nOBX) to anxiety-related behavior as assayed in the elevated plus maze (EPM) as well as the expression of dopaminergic receptors (D1-like, D2-like, and D3) in the NAcc and CPu at pre- and post-pubertal ages in the rat. The results show that nOBX increased the number of entries in the open arm of the EPM post-pubertally, suggesting an anxiolytic-related effect. nOBX increased the D2-like binding in the NAcc shell and D3 binding in the NAcc core pre-pubertally. At post-pubertal ages, the D3 binding was reduced at the olfactory tubercle and islands of Calleja in nOBX rats. Alterations in the DA receptor expression may be one mechanism responsible for the observed behavioral modifications in nOBX rats.
Topics: Rats; Animals; Dopamine; Smell; Receptors, Dopamine; Nucleus Accumbens; Anxiety; Anti-Anxiety Agents; Receptors, Dopamine D1
PubMed: 37132073
DOI: 10.1002/syn.22272 -
Neuroscience Research May 2023The olfactory centres are the evolutionary oldest and most conservative area of the telencephalon. Olfactory deficiencies are involved in a large spectrum of neurologic... (Review)
Review
The olfactory centres are the evolutionary oldest and most conservative area of the telencephalon. Olfactory deficiencies are involved in a large spectrum of neurologic disorders and neurodegenerative diseases. The growing interest in human olfaction has been also been driven by COVID-19-induced transitional anosmia. Nevertheless, recent data on the human olfactory centres concerning normal histology and morphogenesis are rare. Published data in the field are mainly restricted to classic studies with non-uniform nomenclature and varied definitions of certain olfactory areas. While the olfactory system in model animals (rats, mice, and more rarely non-human primates) has been extensively investigated, the developmental timetable of olfactory centres in both human prenatal and postnatal ontogeny are poorly understood and unsystemised, which complicates the process of analysing human material, including medical researches. The main purpose of this review is to provide and discuss relevant morphological data on the normal ontogeny of the human olfactory centres, with a focus on the timetable of maturation and developmental cytoarchitecture, and with special reference to the definitions and terminology of certain olfactory areas.
Topics: Pregnancy; Female; Humans; Rats; Animals; Mice; Smell; COVID-19; Primates; Olfactory Bulb; Olfactory Pathways
PubMed: 36521642
DOI: 10.1016/j.neures.2022.12.005 -
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 -
World Neurosurgery Jan 2023Lesions in the ventral striatum region (above the anterior perforated substance) are a challenge for neurosurgeons due to their direct relationship with the... (Review)
Review
BACKGROUND
Lesions in the ventral striatum region (above the anterior perforated substance) are a challenge for neurosurgeons due to their direct relationship with the lenticulostriate arteries, which difficult the surgical access. The standard approaches for this region include the following: 1) transfrontal approach, 2) transanterior perforating substance approach, 3) transcallosal transventricular approach, and 4) pterional transsylvian-transinsular route. In this study, we aimed to describe a novel anatomical approach through the anterior limiting sulcus of the insula in order to access the ventral striatum.
METHODS
We reviewed the literature and performed a detailed dissection of this region by using Klingler's technique with brain specimens injected with silicone, paying special attention to the white fibers and lenticulostriate arteries, and provided a description of an illustrative case of a cavernous malformation.
RESULTS
Neuroanatomical dissections showed that the lenticulostriate arteries had an inverted C-shaped anterior concavity, leaving less significant vascular relationships in the depth of the anterior limiting sulcus of the insula. In the case we described, the cavernous malformation was completely resected and the patient was discharged without any neurological deficits.
CONCLUSIONS
The transanterior limiting sulcus of the insula approach to the ventral striatum offers a safe access route for selected cases and can be performed on the basis of anatomical references. Three-dimensional understanding of the intrinsic brain architecture and its relationships with vascular structures in this specific area is important and can be acquired mainly through laboratory training.
Topics: Humans; Neurosurgical Procedures; Insular Cortex; Olfactory Tubercle; Dissection; Middle Cerebral Artery
PubMed: 36208868
DOI: 10.1016/j.wneu.2022.09.115 -
Frontiers in Behavioral Neuroscience 2022The methyl-CpG binding protein 2 gene () encodes an epigenetic transcriptional regulator implicated in neuronal plasticity. Loss-of-function mutations in this gene are...
The methyl-CpG binding protein 2 gene () encodes an epigenetic transcriptional regulator implicated in neuronal plasticity. Loss-of-function mutations in this gene are the primary cause of Rett syndrome and, to a lesser degree, of other neurodevelopmental disorders. Recently, we demonstrated that both haploinsuficiency and mild early life stress decrease anxiety-like behaviours and neuronal activation in brain areas controlling these responses in adolescent female mice. Here, we extend this work to males by using -null and wild type adolescent mice subjected to maternal separation and their non-stressed controls. We assessed their behavioural responses in a battery of anxiety-provoking tests. Upon exposure to an elevated plus maze in aversive conditions, we evaluated changes in c-FOS expression in stress- and anxiety-related brain regions. In addition, we assessed the impact of maternal separation in neuronal maturation using doublecortin and reelin as surrogate markers. Mutant males showed reduced motor abilities, increased activation of the olfactory bulbs, probably due to breathing abnormalities, and decreased activation of the paraventricular thalamic nucleus, when compared to wild type mice. In addition, maternal separation increased the number of immature doublecortin-like neurons found in -null animals. Moreover, this work shows for the first time that reelin is decreased in the mutant animals at the olfactory tubercle, piriform cortex and hippocampal dentate gyrus, an effect also associated to maternal separation. Taken together, our results suggest that maternal separation exacerbates some phenotypical alterations associated with lack of MeCP2 in adolescent males.
PubMed: 36082308
DOI: 10.3389/fnbeh.2022.974692 -
Frontiers in Neural Circuits 2022The olfactory tubercle (OT) is a striatal region that receives olfactory inputs. mRNAs of prodynorphin (Pdyn) and preproenkephalin (Penk), precursors of dynorphins and...
The olfactory tubercle (OT) is a striatal region that receives olfactory inputs. mRNAs of prodynorphin (Pdyn) and preproenkephalin (Penk), precursors of dynorphins and enkephalins, respectively, are strongly expressed in the striatum. Both produce opioid peptides with various physiological effects such as pain relief and euphoria. Recent studies have revealed that OT has anatomical and cytoarchitectonic domains that play different roles in odor-induced motivated behavior. Neuronal subtypes of the OT can be distinguished by their expression of the dopamine receptors D1 (Drd1) and D2 (Drd2). Here, we addressed whether and which type of opioid peptide precursors the D1- and D2-expressing neurons in the OT express. We used multiple fluorescence hybridization for mRNAs of the opioid precursors and dopamine receptors to characterize mouse OT neurons. Pdyn was mainly expressed by Drd1-expressing cells in the dense cell layer (DCL) of the OT, whereas Penk was expressed primarily by Drd2-expressing cells in the DCL. We also confirmed the presence of a larger population of Pdyn-Penk-Drd1 co-expressing cells in the DCL of the anteromedial OT compared with the anterolateral OT. These observations will help understand whether and how dynorphins and enkephalins in the OT are involved in diverse odor-induced motivated behaviors.
Topics: Animals; Corpus Striatum; Dynorphins; Enkephalins; In Situ Hybridization, Fluorescence; Mice; Neurons; Olfactory Tubercle; Protein Precursors; RNA, Messenger; Receptors, Dopamine D1
PubMed: 35937204
DOI: 10.3389/fncir.2022.908964 -
ELife Jun 2022Positive and negative associations acquired through olfactory experience are thought to be especially strong and long-lasting. The conserved direct olfactory sensory...
Positive and negative associations acquired through olfactory experience are thought to be especially strong and long-lasting. The conserved direct olfactory sensory input to the ventral striatal olfactory tubercle (OT) and its convergence with dense dopaminergic input to the OT could underlie this privileged form of associative memory, but how this process occurs is not well understood. We imaged the activity of the two canonical types of striatal neurons, expressing D1- or D2-type dopamine receptors, in the OT at cellular resolution while mice learned odor-outcome associations ranging from aversive to rewarding. D1 and D2 neurons both responded to rewarding and aversive odors. D1 neurons in the OT robustly and bidirectionally represented odor valence, responding similarly to odors predicting similar outcomes regardless of odor identity. This valence representation persisted even in the absence of a licking response to the odors and in the absence of the outcomes, indicating a true transformation of odor sensory information by D1 OT neurons. In contrast, D2 neuronal representation of the odor-outcome associations was weaker, contingent on a licking response by the mouse, and D2 neurons were more selective for odor identity than valence. Stimulus valence coding in the OT was modality-sensitive, with separate sets of D1 neurons responding to odors and sounds predicting the same outcomes, suggesting that integration of multimodal valence information happens downstream of the OT. Our results point to distinct representation of identity and valence of odor stimuli by D1 and D2 neurons in the OT.
Topics: Animals; Cues; Mice; Neurons; Odorants; Olfactory Tubercle; Receptors, Dopamine D2; Smell; Ventral Striatum
PubMed: 35708179
DOI: 10.7554/eLife.75463