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The Journal of Comparative Neurology Feb 2016Although the hippocampus is structurally quite different among reptiles, birds, and mammals, its function in spatial memory is said to be highly conserved. This is... (Review)
Review
Although the hippocampus is structurally quite different among reptiles, birds, and mammals, its function in spatial memory is said to be highly conserved. This is surprising, given that structural differences generally reflect functional differences. Here I review this enigma in some detail, identifying several evolutionary changes in hippocampal cytoarchitecture and connectivity. I recognize a lepidosaurid pattern of hippocampal organization (in lizards, snakes, and the tuatara Sphenodon) that differs substantially from the pattern of organization observed in the turtle/archosaur lineage, which includes crocodilians and birds. Although individual subdivisions of the hippocampus are difficult to homologize between these two patterns, both lack a clear homolog of the mammalian dentate gyrus. The strictly trilaminar organization of the ancestral amniote hippocampus was gradually lost in the lineage leading to birds, and birds expanded the system of intrahippocampal axon collaterals, relative to turtles and lizards. These expanded collateral axon branches resemble the extensive collaterals in CA3 of the mammalian hippocampus but probably evolved independently of them. Additional examples of convergent evolution between birds and mammals are the loss of direct inputs to the hippocampus from the primary olfactory cortex and the general expansion of telencephalic regions that communicate reciprocally with the hippocampus. Given this structural convergence, it seems likely that some similarities in the function of the hippocampus between birds and mammals, notably its role in the ability to remember many different locations without extensive training, likewise evolved convergently. The currently available data do not allow for a strong test of this hypothesis, but the hypothesis itself suggests some promising new research directions.
Topics: Animals; Biological Evolution; Birds; Hippocampus; Neural Pathways; Neurons; Reptiles
PubMed: 25982694
DOI: 10.1002/cne.23803 -
Frontiers in Neuroscience 2023
PubMed: 38249580
DOI: 10.3389/fnins.2023.1307844 -
Brain Communications 2020The orbitofrontal cortex in primates including humans is the key brain area in emotion, and in the representation of reward value and in non-reward, that is not... (Review)
Review
The orbitofrontal cortex in primates including humans is the key brain area in emotion, and in the representation of reward value and in non-reward, that is not obtaining an expected reward. Cortical processing before the orbitofrontal cortex is about the identity of stimuli, i.e. 'what' is present, and not about reward value. There is evidence that this holds for taste, visual, somatosensory and olfactory stimuli. The human medial orbitofrontal cortex represents many different types of reward, and the lateral orbitofrontal cortex represents non-reward and punishment. Not obtaining an expected reward can lead to sadness, and feeling depressed. The concept is advanced that an important brain region in depression is the orbitofrontal cortex, with depression related to over-responsiveness and over-connectedness of the non-reward-related lateral orbitofrontal cortex, and to under-responsiveness and under-connectivity of the reward-related medial orbitofrontal cortex. Evidence from large-scale voxel-level studies and supported by an activation study is described that provides support for this hypothesis. Increased functional connectivity of the lateral orbitofrontal cortex with brain areas that include the precuneus, posterior cingulate cortex and angular gyrus is found in patients with depression and is reduced towards the levels in controls when treated with medication. Decreased functional connectivity of the medial orbitofrontal cortex with medial temporal lobe areas involved in memory is found in patients with depression. Some treatments for depression may act by reducing activity or connectivity of the lateral orbitofrontal cortex. New treatments that increase the activity or connectivity of the medial orbitofrontal cortex may be useful for depression. These concepts, and that of increased activity in non-reward attractor networks, have potential for advancing our understanding and treatment of depression. The focus is on the orbitofrontal cortex in primates including humans, because of differences of operation of the orbitofrontal cortex, and indeed of reward systems, in rodents. Finally, the hypothesis is developed that the orbitofrontal cortex has a special role in emotion and decision-making in part because as a cortical area it can implement attractor networks useful in maintaining reward and emotional states online, and in decision-making.
PubMed: 33364600
DOI: 10.1093/braincomms/fcaa196 -
Translational Psychiatry Mar 2021Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI)...
Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.
Topics: Brain; Dementia; Depression; Hippocampus; Humans; Magnetic Resonance Imaging; Olfaction Disorders; Temporal Lobe
PubMed: 33731679
DOI: 10.1038/s41398-021-01291-0 -
Brain Research Aug 2016In the early 1980's, the dispute on the existence of a multiplicity of receptors for neurotransmitter was at its height. Several subtypes of serotonin (5-HT) receptors... (Review)
Review
UNLABELLED
In the early 1980's, the dispute on the existence of a multiplicity of receptors for neurotransmitter was at its height. Several subtypes of serotonin (5-HT) receptors were proposed on the basis of radioligand binding assays. In order to provide further support to the existence of these receptors we performed quantitative autoradiographic mapping of the binding of several ligands for the 5-HT1 receptor labeling the subtypes 5-HT1A, 5-HT1B and 5-HT1C, and characterized pharmacologically these different receptors. The results demonstrated differential localization of the subtypes of 5-HT1 receptors indicating that they were expressed by different cell populations, probably neurons, in the brain and further supporting their reality. Shortly afterwards, the cloning of the genes coding for these 5-HT receptors, and many others, ended the dispute by demonstrating that they were different proteins. The advent of Molecular Biology provided new methodologies for the study of the chemical and molecular anatomy of 5-HT receptors in brain, by visualizing cells expressing their mRNA by in situ hybridization and showed that the family of mammalian 5-HT receptors has 14 members, a figure much larger than ever suspected at that time.
ORIGINAL ARTICLE ABSTRACT
QUANTITATIVE AUTORADIOGRAPHIC MAPPING OF SEROTONIN RECEPTORS IN THE RAT BRAIN. I. SEROTONIN-1 RECEPTORS: The distribution of serotonin-1 (5-HT1) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with [(3)H]serotonin (5-[(3)H]HT), 8-hydroxy-2-[H-dipropylamino-(3)H]tetralin (8-OH-[(3)H]DPAT), [(3)H]LSD and [(3)H]mesulergine, and the densities quantified by microdensitometry with the aid of a computer-assisted image-analysis system. Competition experiments for 5-[(3)H]HT binding by several serotonin-1 agonizts led to the identification of brain areas enriched in each one of the three subtypes of 5-HT1 recognition sites already described (5-HT1A, 5-HT1B, 5-HT1C). The existence of these׳selective׳ areas allowed a detailed pharmacological characterization of these sites to be made in a more precise manner than has been attained in membrane-binding studies. While 5-[(3)H]HT labeled with nanomolar affinity all the 5-HT1 subtypes, the other (3)H-labeled ligands labeled selectively 5-HT1A (8-OH-[(3)H]DPAT), 5-HT1C ([(3)H]mesulergine) and both of them ([(3)H]LSD). Very high concentrations of 5-HT1 receptors were localized in the choroid plexus, lateroseptal nucleus, globus pallidus and ventral pallidum, dentate gyrus, dorsal subiculum, olivary pretectal nucleus, substantia nigra, reticular and external layer of the entorhinal cortex. The different fields of the hippocampus (CA1-CA4), some nuclei of the amygdaloid complex, the hypothalamic nuclei and the dorsal raphé, among others, also presented high concentrations of sites. Areas containing intermediate densities of 5-HT1 receptors included the claustrum, olfactory tubercle, accumbens, central gray and lateral cerebellar nucleus. The nucleus caudate-putamen and the cortex, at the different levels studied, presented receptor densities ranging from intermediate to low. Finally, in other brain areas-pons, medulla, and spinal cord-only low or very low concentrations of 5-HT1 receptors were found. From the areas strongly enriched in 5-HT1 sites, dentate gyrus and septal nucleus contained 5-HT1A sites, while globus pallidus, dorsal subiculum, substantia nigra and olivary pretectal nucleus were enriched in 5-HT1B. The sites in the choroid plexus, which presented the highest density of receptors in the rat brain, were of the 5-HT1C subtype. The distribution of 5-HT1 receptors reported here is discussed in correlation with the distribution of serotoninergic neurons and fibers, the related anatomical pathways and the effects which appear to be mediated by these sites. © 1985.This article is part of a Special Issue entitled SI:50th Anniversary Issue. This article is part of a Special Issue entitled SI:50th Anniversary Issue.
Topics: Animals; Autoradiography; Brain; Choroid Plexus; History, 20th Century; Humans; In Situ Hybridization; Neurons; Neurosciences; Rats; Receptors, Serotonin, 5-HT1
PubMed: 26740406
DOI: 10.1016/j.brainres.2015.12.042 -
Journal of Affective Disorders Jun 2022Odor identification (OI) impairment increases the risk of Alzheimer's disease and brain abnormalities in patients with late-life depression (LLD). However, it remains...
BACKGROUND
Odor identification (OI) impairment increases the risk of Alzheimer's disease and brain abnormalities in patients with late-life depression (LLD). However, it remains unclear whether abnormal functional connectivity (FC) of olfactory regions is involved in the relationship between OI impairment and dementia risk in LLD patients. The current study aims to explore the olfactory FC patterns of LLD patients and how olfactory FCs mediate the relationship between OI and cognition.
METHODS
A total of 150 participants underwent resting-state functional magnetic resonance imaging and psychometric and olfactory assessments. The primary and secondary olfactory regions were selected as regions of interest to investigate olfactory FC patterns and their association with OI and cognitive performance in LLD patients.
RESULTS
Compared with LLD patients without OI impairment and normal controls, LLD patients with OI impairment exhibited increased FC between the left orbital frontal cortex (OFC) and left calcarine gyrus, between the left OFC and right lingual gyrus, between the right OFC and right rectus gyrus, and decreased FC between the right piriform cortex and right superior parietal lobule. Additionally, these abnormal FCs were associated with scores of OI, global cognition and language function. Finally, the FC between the right piriform cortex and right superior parietal lobule exhibited a partially mediated effect on the relationship between OI and MMSE scores.
LIMITATIONS
The present study did not exclude the possible effect of drugs.
CONCLUSION
LLD patients with OI impairment exhibited more disrupted olfactory FC (a decrease in the primary olfactory cortex and an increase in the secondary olfactory cortex) than LLD patients with intact OI, and these abnormal FCs may serve as potential targets for neuromodulation in LLD patients to prevent them from developing dementia.
Topics: Alzheimer Disease; Depression; Humans; Magnetic Resonance Imaging; Prefrontal Cortex; Smell
PubMed: 35292309
DOI: 10.1016/j.jad.2022.03.014 -
Reviews in the Neurosciences Dec 2022There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a... (Review)
Review
There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a time scale of tens of ms. If such assemblies form an odor representation, then a fundamental question is how each assembly then induces neuronal activity in downstream structures. We have addressed this question in a detailed model of superficial layers of lateral entorhinal cortex, a recipient of input from olfactory cortex and olfactory bulb. Our results predict that the response of the fan cell subpopulation can be approximated by a relatively simple Boolean process, somewhat along the lines of the McCulloch/Pitts scheme; this is the case because of the sparsity of recurrent excitation amongst fan cells. However, because of recurrent excitatory connections between layer 2 and layer 3 pyramidal cells, synaptic and probably also gap junctional, the response of pyramidal cell subnetworks cannot be so approximated. Because of the highly structured anatomy of entorhinal output projections, our model suggests that downstream targets of entorhinal cortex (dentate gyrus, hippocampal CA3, CA1, piriform cortex, olfactory bulb) receive differentially processed information.
Topics: Humans; Entorhinal Cortex; Hippocampus; Neurons; Pyramidal Cells
PubMed: 35447022
DOI: 10.1515/revneuro-2022-0011 -
Neural Regeneration Research Jan 2024Adult neurogenesis, the process of creating new neurons, involves the coordinated division, migration, and differentiation of neural stem cells. This process is... (Review)
Review
Adult neurogenesis, the process of creating new neurons, involves the coordinated division, migration, and differentiation of neural stem cells. This process is restricted to neurogenic niches located in two distinct areas of the brain: the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle, where new neurons are generated and then migrate to the olfactory bulb. Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells. Interestingly, recent years have seen tremendous progress in our understanding of adult brain neurogenesis, bridging the knowledge gap between embryonic and adult neurogenesis. Here, we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells. In this notion, we talk about the importance of intracellular signaling molecules in mobilizing endogenous neural stem cell proliferation. Based on the current understanding, we can declare that these molecules play a role in targeting neurogenesis in the mature brain. However, to achieve this goal, we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints, which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.
PubMed: 37488837
DOI: 10.4103/1673-5374.375317 -
PeerJ 2020Altered cerebral blood flow (CBF) and amplitude of low-frequency fluctuation (ALFF) have been reported in hemodialysis patients. However, neurovascular coupling...
BACKGROUND
Altered cerebral blood flow (CBF) and amplitude of low-frequency fluctuation (ALFF) have been reported in hemodialysis patients. However, neurovascular coupling impairments, which provide a novel insight into the human brain, have not been reported in hemodialysis patients.
METHODS
We combined arterial spin labeling (ASL) and blood oxygen level dependent (BOLD) techniques to investigate neurovascular coupling alterations and its relationships with demographic and clinical data in 46 hemodialysis patients and 47 healthy controls. To explore regional neuronal activity, ALFF was obtained from resting-state functional MRI. To measure cerebral vascular response, CBF was calculated from ASL. The across-voxel CBF-ALFF correlations for global neurovascular coupling and CBF/ALFF ratio for regional neurovascular coupling were compared between hemodialysis patients and healthy controls. Two-sample -tests were used to compare the intergroup differences in CBF and ALFF. Multiple comparisons were corrected using a voxel-wise false discovery rate (FDR) method ( < 0.05).
RESULTS
All hemodialysis patients and healthy controls showed significant across-voxel correlations between CBF and ALFF. Hemodialysis patients showed a significantly reduced global CBF-ALFF coupling ( = 0.0011) compared to healthy controls at the voxel-level. Of note, decreased CBF/ALFF ratio was exclusively located in the bilateral amygdala involved in emotional regulation and cognitive processing in hemodialysis patients. In hemodialysis patients, the decreased CBF (right olfactory cortex, anterior cingulate gyrus and bilateral insula) and ALFF (bilateral precuneus and superior frontal gyrus) were mainly located in the default mode network and salience network-related regions as well as increased CBF in the bilateral thalamus.
CONCLUSIONS
These novel findings reveal that disrupted neurovascular coupling may be a potential neural mechanism in hemodialysis patients.
PubMed: 32328355
DOI: 10.7717/peerj.8989 -
Current Topics in Developmental Biology 2017T-box transcription factors play key roles in the regulation of developmental processes such as cell differentiation and migration. Mammals have 17 T-box genes, of which... (Review)
Review
T-box transcription factors play key roles in the regulation of developmental processes such as cell differentiation and migration. Mammals have 17 T-box genes, of which several regulate brain development. The Tbr1 subfamily of T-box genes is particularly important in development of the cerebral cortex, olfactory bulbs (OBs), and cerebellum. This subfamily is comprised of Tbr1, Tbr2 (also known as Eomes), and Tbx21. In developing cerebral cortex, Tbr2 and Tbr1 are expressed during successive stages of differentiation in the pyramidal neuron lineage, from Tbr2+ intermediate progenitors to Tbr1+ postmitotic glutamatergic neurons. At each stage, Tbr2 and Tbr1 regulate laminar and regional identity of cortical projection neurons, cell migration, and axon guidance. In the OB, Tbr1 subfamily genes regulate neurogenesis of mitral and tufted cells, and glutamatergic juxtaglomerular interneurons. Tbr2 is also prominent in the development of retinal ganglion cells in nonimage-forming pathways. Other regions that require Tbr2 or Tbr1 in development or adulthood include the cerebellum and adult dentate gyrus. In humans, de novo mutations in TBR1 are important causes of sporadic autism and intellectual disability. Further studies of T-box transcription factors will enhance our understanding of neurodevelopmental disorders and inform approaches to new therapies.
Topics: Amino Acid Sequence; Animals; Brain; Humans; Models, Biological; Mutation; Neurogenesis; Neurons; T-Box Domain Proteins
PubMed: 28057268
DOI: 10.1016/bs.ctdb.2016.08.001