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Neuron Oct 2023One of the most captivating questions in neuroscience revolves around the brain's ability to efficiently and durably capture and store information. It must process... (Review)
Review
One of the most captivating questions in neuroscience revolves around the brain's ability to efficiently and durably capture and store information. It must process continuous input from sensory organs while also encoding memories that can persist throughout a lifetime. What are the cellular-, subcellular-, and network-level mechanisms that underlie this remarkable capacity for long-term information storage? Furthermore, what contributions do distinct types of GABAergic interneurons make to this process? As the hippocampus plays a pivotal role in memory, our review focuses on three aspects: (1) delineation of hippocampal interneuron types and their connectivity, (2) interneuron plasticity, and (3) activity patterns of interneurons during memory-related rhythms, including the role of long-range interneurons and disinhibition. We explore how these three elements, together showcasing the remarkable diversity of inhibitory circuits, shape the processing of memories in the hippocampus.
Topics: Interneurons; Hippocampus
PubMed: 37467748
DOI: 10.1016/j.neuron.2023.06.016 -
Nature Reviews. Neuroscience Aug 2023There has been considerable speculation regarding the function of the dentate gyrus (DG) - a subregion of the mammalian hippocampus - in learning and memory. In this... (Review)
Review
There has been considerable speculation regarding the function of the dentate gyrus (DG) - a subregion of the mammalian hippocampus - in learning and memory. In this Perspective article, we compare leading theories of DG function. We note that these theories all critically rely on the generation of distinct patterns of activity in the region to signal differences between experiences and to reduce interference between memories. However, these theories are divided by the roles they attribute to the DG during learning and recall and by the contributions they ascribe to specific inputs or cell types within the DG. These differences influence the information that the DG is thought to impart to downstream structures. We work towards a holistic view of the role of DG in learning and memory by first developing three critical questions to foster a dialogue between the leading theories. We then evaluate the extent to which previous studies address our questions, highlight remaining areas of conflict, and suggest future experiments to bridge these theories.
Topics: Animals; Humans; Dentate Gyrus; Hippocampus; Mental Recall; Learning; Mammals
PubMed: 37316588
DOI: 10.1038/s41583-023-00710-z -
Frontiers in Immunology 2023Adult hippocampal neurogenesis generates functional neurons from neural progenitor cells in the hippocampal dentate gyrus (DG) to complement and repair neurons and... (Review)
Review
Adult hippocampal neurogenesis generates functional neurons from neural progenitor cells in the hippocampal dentate gyrus (DG) to complement and repair neurons and neural circuits, thus benefiting the treatment of depression. Increasing evidence has shown that aberrant microglial activity can disrupt the appropriate formation and development of functional properties of neurogenesis, which will play a crucial role in the occurrence and development of depression. However, the mechanisms of the crosstalk between microglia and adult hippocampal neurogenesis in depression are not yet fully understood. Therefore, in this review, we first introduce recent discoveries regarding the roles of microglia and adult hippocampal neurogenesis in the etiology of depression. Then, we systematically discuss the possible mechanisms of how microglia regulate adult hippocampal neurogenesis in depression according to recent studies, which involve toll-like receptors, microglial polarization, fractalkine-C-X3-C motif chemokine receptor 1, hypothalamic-pituitary-adrenal axis, cytokines, brain-derived neurotrophic factor, and the microbiota-gut-brain axis, etc. In addition, we summarize the promising drugs that could improve the adult hippocampal neurogenesis by regulating the microglia. These findings will help us understand the complicated pathological mechanisms of depression and shed light on the development of new treatment strategies for this disease.
Topics: Depression; Microglia; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Hippocampus; Neurogenesis
PubMed: 37881439
DOI: 10.3389/fimmu.2023.1193053 -
Science (New York, N.Y.) Oct 2023Episodic memory involves learning and recalling associations between items and their spatiotemporal context. Those memories can be further used to generate internal...
Episodic memory involves learning and recalling associations between items and their spatiotemporal context. Those memories can be further used to generate internal models of the world that enable predictions to be made. The mechanisms that support these associative and predictive aspects of memory are not yet understood. In this study, we used an optogenetic manipulation to perturb the sequential structure, but not global network dynamics, of place cells as rats traversed specific spatial trajectories. This perturbation abolished replay of those trajectories and the development of predictive representations, leading to impaired learning of new optimal trajectories during memory-guided navigation. However, place cell assembly reactivation and reward-context associative learning were unaffected. Our results show a mechanistic dissociation between two complementary hippocampal codes: an associative code (through coactivity) and a predictive code (through sequences).
Topics: Animals; Rats; Conditioning, Classical; Hippocampus; Memory, Episodic; Mental Recall; Optogenetics; Theta Rhythm; Male; Rats, Long-Evans; Association Learning
PubMed: 37856604
DOI: 10.1126/science.adi8237 -
Cells Nov 2023Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated... (Review)
Review
Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic-pituitary-adrenal (HPA) axis, a vital neuroendocrine system responsible for stress response and maintaining homeostasis. Disruptions in cortisol regulation due to chronic stress, disease, and aging have profound implications for multiple bodily systems. Animal models have been instrumental in elucidating these complex cortisol dynamics during stress, shedding light on the interplay between physiological, neuroendocrine, and immune factors in the stress response. These models have also revealed the impact of various stressors, including social hierarchies, highlighting the role of social factors in cortisol regulation. Moreover, chronic stress is closely linked to the progression of neurodegenerative diseases, like Alzheimer's and Parkinson's, driven by excessive cortisol production and HPA axis dysregulation, along with neuroinflammation in the central nervous system. The relationship between cortisol dysregulation and major depressive disorder is complex, characterized by HPA axis hyperactivity and chronic inflammation. Lastly, chronic pain is associated with abnormal cortisol patterns that heighten pain sensitivity and susceptibility. Understanding these multifaceted mechanisms and their effects is essential, as they offer insights into potential interventions to mitigate the detrimental consequences of chronic stress and cortisol dysregulation in these conditions.
Topics: Animals; Hydrocortisone; Depressive Disorder, Major; Neurodegenerative Diseases; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 38067154
DOI: 10.3390/cells12232726 -
Brain Structure & Function Jun 2023The orbitofrontal cortex and amygdala are involved in emotion and in motivation, but the relationship between these functions performed by these brain structures is not... (Review)
Review
The orbitofrontal cortex and amygdala are involved in emotion and in motivation, but the relationship between these functions performed by these brain structures is not clear. To address this, a unified theory of emotion and motivation is described in which motivational states are states in which instrumental goal-directed actions are performed to obtain rewards or avoid punishers, and emotional states are states that are elicited when the reward or punisher is or is not received. This greatly simplifies our understanding of emotion and motivation, for the same set of genes and associated brain systems can define the primary or unlearned rewards and punishers such as sweet taste or pain. Recent evidence on the connectivity of human brain systems involved in emotion and motivation indicates that the orbitofrontal cortex is involved in reward value and experienced emotion with outputs to cortical regions including those involved in language, and is a key brain region involved in depression and the associated changes in motivation. The amygdala has weak effective connectivity back to the cortex in humans, and is implicated in brainstem-mediated responses to stimuli such as freezing and autonomic activity, rather than in declarative emotion. The anterior cingulate cortex is involved in learning actions to obtain rewards, and with the orbitofrontal cortex and ventromedial prefrontal cortex in providing the goals for navigation and in reward-related effects on memory consolidation mediated partly via the cholinergic system.
Topics: Humans; Gyrus Cinguli; Motivation; Emotions; Amygdala; Prefrontal Cortex; Reward
PubMed: 37178232
DOI: 10.1007/s00429-023-02644-9 -
Science Advances Jun 2023It is known that post-retrieval extinction but not extinction alone could erase fear memory. However, whether the coding pattern of original fear engrams is remodeled or...
It is known that post-retrieval extinction but not extinction alone could erase fear memory. However, whether the coding pattern of original fear engrams is remodeled or inhibited remains largely unclear. We found increased reactivation of engram cells in the prelimbic cortex and basolateral amygdala during memory updating. Moreover, conditioned stimulus- and unconditioned stimulus-initiated memory updating depends on the engram cell reactivation in the prelimbic cortex and basolateral amygdala, respectively. Last, we found that memory updating causes increased overlapping between fear and extinction cells, and the original fear engram encoding was altered during memory updating. Our data provide the first evidence to show the overlapping ensembles between fear and extinction cells and the functional reorganization of original engrams underlying conditioned stimulus- and unconditioned stimulus-initiated memory updating.
Topics: Memory; Fear; Conditioning, Classical; Basolateral Nuclear Complex; Conditioning, Operant
PubMed: 37285430
DOI: 10.1126/sciadv.adf0284 -
Nature Sep 2023Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive...
Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus and converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.
Topics: Humans; Body Mass Index; Cohort Studies; Cues; Electrophysiology; Evoked Potentials; Feeding and Eating Disorders; Feeding Behavior; Food; Hippocampus; Obesity; Orexins; Neural Pathways
PubMed: 37648849
DOI: 10.1038/s41586-023-06459-w