Spatialization of Time in the Entorhinal-Hippocampal System

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.807197 ◽

2022 ◽

Vol 15 ◽

Author(s):

Troy M. Houser

Keyword(s):

Empirical Evidence ◽

Functional Role ◽

Spatial Representation ◽

Computational Models ◽

Spatial Information ◽

Cognitive Representations ◽

Hippocampal Activity ◽

The Brain

The functional role of the entorhinal-hippocampal system has been a long withstanding mystery. One key theory that has become most popular is that the entorhinal-hippocampal system represents space to facilitate navigation in one’s surroundings. In this Perspective article, I introduce a novel idea that undermines the inherent uniqueness of spatial information in favor of time driving entorhinal-hippocampal activity. Specifically, by spatializing events that occur in succession (i.e., across time), the entorhinal-hippocampal system is critical for all types of cognitive representations. I back up this argument with empirical evidence that hints at a role for the entorhinal-hippocampal system in non-spatial representation, and computational models of the logarithmic compression of time in the brain.

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The potential role for sphingolipids in neuropathogenesis of Alzheimer’s disease

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20135901025 ◽

2013 ◽

Vol 59 (1) ◽

pp. 25-50 ◽

Cited By ~ 12

Author(s):

A.V. Alessenko

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Functional Role ◽

Potential Role ◽

Early Stage ◽

New Drugs ◽

Neuronal Function ◽

Sphingosine 1 Phosphate ◽

The Brain

The review discusses the functional role of sphingolipids in the pathogenesis of Alzheimer's disease. Certain evidence exist that the imbalance of sphingolipids such as sphingomyelin, ceramide, sphingosine, sphingosine-1-phosphate and galactosylceramide in the brain of animals and humans, in the cerebrospinal fluid and blood plasma of patients with Alzheimer's disease play a crucial role in neuronal function by regulating growth, differentiation and cell death in CNS. Activation of sphingomyelinase, which leads to the accumulation of the proapoptotic agent, ceramide, can be considered as a new mechanism for AD and may be a prerequisite for the treatment of this disease by using drugs that inhibit sphingomyelinase activity. The role of sphingolipids as biomarkers for the diagnosis of the early stage of Alzheimer's disease and monitoring the effectiveness of treatment with new drugs is discussed.

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Avoidance response to CO2 in the lateral horn

10.1101/342675 ◽

2018 ◽

Author(s):

Nélia Varela ◽

Miguel Gaspar ◽

Sophie Dias ◽

Maria Luísa Vasconcelos

Keyword(s):

Calcium Imaging ◽

Mushroom Body ◽

Antennal Lobe ◽

Functional Role ◽

Direct Evidence ◽

Physiological Responses ◽

Lateral Horn ◽

The One ◽

The Brain

ABSTRACTIn flies, the olfactory information is carried from the first relay in the brain, the antennal lobe, to the mushroom body (MB) and the lateral horn (LH). Olfactory associations are formed in the MB. The LH was ascribed a role in innate responses based on the stereotyped connectivity with the antennal lobe, stereotyped physiological responses to odors and MB silencing experiments. Direct evidence for the functional role of the LH is still missing. Here we investigate the behavioral role of the LH neurons directly, using the CO2 response as a paradigm. Our results show the involvement of the LH in innate responses. Specifically, we demonstrate that activity in two sets of neurons is required for the full behavioral response to CO2. Using calcium imaging we observe that the two sets of neurons respond to CO2 in different manners. Using independent manipulation and recording of the two sets of neurons we find that the one that projects to the SIP also outputs to the local neurons within the LH. The design of simultaneous output at the LH and the SIP, an output of the MB, allows for coordination between innate and learned responses.

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Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter

10.1101/443531 ◽

2018 ◽

Author(s):

Miho Sato-Hashimoto ◽

Tomomi Nozu ◽

Riho Toriba ◽

Ayano Horikoshi ◽

Miho Akaike ◽

...

Keyword(s):

White Matter ◽

Membrane Protein ◽

Functional Role ◽

Regulatory Protein ◽

Genetic Ablation ◽

Brain White Matter ◽

Expression Of Genes ◽

The Brain ◽

Repair Phase

AbstractA characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage in the white matter, but resulted in the increased expression of genes characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

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Abstract 083: Role of Endoplasmic Reticulum Stress in the Subfornical Organ (SFO) in Fluid Balance and Metabolic Effects of Brain Renin-Angiotensin System (RAS) Activation

Hypertension ◽

10.1161/hyp.64.suppl_1.083 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Fusakazu Jo ◽

Hiromi Jo ◽

Aline M Hilzendeger ◽

Martin D Cassell ◽

D. T Rutkowski ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

Water Intake ◽

Fluid Balance ◽

Functional Role ◽

Metabolic Effects ◽

Chemical Chaperone ◽

Reduced Drinking ◽

The Brain

Endoplasmic reticulum (ER) stress has been identified as an important contributor to neurological diseases and implicated in mediating hypothalamic inflammation and the hypertensive effects of angiotensin II (AngII). We examined the role of ER stress in the metabolic and fluid balance effects of brain AngII in two mouse models: 1) sRA transgenic mice (expressing human renin in neurons and human angiotensinogen in glia and neurons), and 2) DOCA-salt treated C57BL/6J mice. Both DOCA-salt and sRA mice exhibit hyperactivity of the brain RAS, suppression of circulating RAS, hypertension, polydipsia, and an elevated resting metabolic rate (RMR). CCAAT-enhancer-binding protein homologous protein (CHOP), a marker of chronic ER stress, was examined by immunocytochemistry in the brain of both models. CHOP immunoreactivity was evident in the SFO of sRA and DOCA-salt mice but was absent in control and CHOP-/- mice. We infused the ER stress-reducing chemical chaperone tauroursodeoxycholic acid (TUDCA, 5.28 ug/day, or aCSF vehicle) to assess if ER stress is mechanistically related to the hypertension, polydipsia, and elevated RMR observed in both models. In initial studies, ICV TUDCA significantly attenuated the polydipsia (aCSF 20.7±0.9 vs TUDCA 10.8±1.0 mL/day, n=6,2) and RMR (aCSF, 3.38±0.07 vs TUDCA 3.16±0.06 mL O2/100g/min, P<0.05 n=13,11) in the DOCA-salt model. ICV TUDCA had similar effects on the polydipsia in the sRA model (51±10% of aCSF control, P<0.05 n=3,4). In the DOCA-salt model, daily ICV injections of TUDCA (10 days, 5ug/ul) markedly reduced drinking, but polydipsia returned one day after the injections were terminated (n=14,12). Daily ICV injection of another ER stress reducer 4-phenylbutyrate (5ug/ul) also reduced drinking (P<0.05 n=5,4). To assess the functional role of CHOP, we measured RMR and water intake in CHOP-/- mice. Interestingly, CHOP-/- mice exhibited increased baseline RMR (CHOP-/- 0.161±0.010 vs C57 0.140±0.005 kcal/hr, P<0.05 n=10,9). The increase in water intake in response to DOCA-salt was blunted (32.7±0.5 vs 22.8±1.1 ml/day, P<0.05, n=4,5) in CHOP-/- mice. Together these data mechanistically implicate ER stress in the fluid and metabolic responses to increased brain RAS activity and suggest CHOP may play a functional role.

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Corticotropin-releasing hormone signals adversity in both the placenta and the brain: regulation by glucocorticoids and allostatic overload

Journal of Endocrinology ◽

10.1677/joe.0.1610349 ◽

1999 ◽

Vol 161 (3) ◽

pp. 349-356 ◽

Cited By ~ 23

Author(s):

J Schulkin

Keyword(s):

Gene Expression ◽

Preterm Labor ◽

Functional Role ◽

Stria Terminalis ◽

Corticotropin Releasing Hormone ◽

Bed Nucleus ◽

Releasing Hormone ◽

The Brain ◽

Hormone Signals

Glucocorticoids regulate corticotropin-releasing hormone (CRH) gene expression in the placenta and the brain. In both the placenta and two extrahypothalamic sites in the brain (the amygdala and the bed nucleus of the stria terminalis), glucocorticoids elevate CRH gene expression. One functional role of the elevation of CRH by glucocorticoids may be to signal adversity. When CRH is over-expressed in the placenta, it may indicate that the pregnancy is in danger, and preterm labor may result. When CRH is over-expressed in the brains of animals, they may become more fearful. Both situations possibly reflect allostatic mechanisms and vulnerability to allostatic overload, a condition in which biological tissue may be compromised.

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Neuron-specific expression of human angiotensinogen in brain causes increased salt appetite

Physiological Genomics ◽

10.1152/physiolgenomics.00007.2002 ◽

2002 ◽

Vol 9 (2) ◽

pp. 113-120 ◽

Cited By ~ 34

Author(s):

Satoshi Morimoto ◽

Martin D. Cassell ◽

Curt D. Sigmund

Keyword(s):

Functional Role ◽

Salt Intake ◽

Pressor Response ◽

Renin Angiotensin System ◽

Electrolyte Balance ◽

Salt Appetite ◽

Specific Expression ◽

The Brain

The brain renin-angiotensin system (RAS) has an important role in the regulation of cardiovascular function. In the brain, angiotensinogen (AGT) is expressed mainly in astrocytes (glia) and in some neurons in regions controlling cardiovascular activities. Because of the inability to dissect the functional role of astrocyte- vs. neuron-derived AGT in vivo by pharmacological approaches, the exact role of neuron-derived AGT in the regulation of blood pressure (BP) and fluid and electrolyte balance remains unclear. Therefore, we generated a transgenic mouse model overexpressing human AGT under the control of a neuron-specific (synapsin I) promoter (SYN-hAGT). These mice exhibited high-level expression of human AGT mRNA in the brain, with lower expression in the kidney and heart. Human AGT was not detected in plasma, but in the brain it was expressed exclusively in neurons. Intracerebroventricular (30 ng) but not intravenous (500 ng) injection of purified human renin (hREN) caused a pressor response, which was prevented by intracerebroventricular preinjection of the angiotensin II type 1 receptor antagonist losartan, indicating an AT1 receptor-dependent functional role of neuron-derived AGT in the regulation of BP in response to exogenous REN. Double transgenic mice expressing both the hREN gene and SYN-hAGT transgene exhibited normal BP and water intake but had an increased preference for salt. These data suggest that neuronal AGT may play an important role in regulating salt intake and salt appetite.

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Electrical synapses and transient signals in feedforward canonical circuits

10.1101/394593 ◽

2018 ◽

Author(s):

Tuan Pham ◽

Julie S. Haas

Keyword(s):

Signal Processing ◽

Computational Models ◽

Transient Signal ◽

Electrical Synapses ◽

Transient Signals ◽

Network Information ◽

Growing Body ◽

Neuronal Processing ◽

The Brain

AbstractAs information about the world traverses the brain, the signals exchanged between neurons are passed and modulated by synapses, or specialized contacts between neurons. While neurotransmitter-based synapses tend to be either relay excitatory or inhibitory pulses of influence on the postsynaptic neuron, electrical synapses, composed of plaques of gap junction channels, are always-on transmitters that can either excite or inhibit a coupled neighbor. A growing body of evidence indicates that electrical synapses, similar to their chemical counterparts, are modified in strength during physiological neuronal activity. The synchronizing role of electrical synapses in neuronal oscillations has been well established, but their impact on transient signal processing in the brain is much less understood. Here we constructed computational models based on the canonical feedforward neuronal circuit, and included electrical synapses between inhibitory interneurons. We provided discrete closely-timed inputs to the circuits, and characterize the influence of electrical synapses on both the subthreshold summation and spike trains in the output neuron. Our simulations highlight the diverse and powerful roles that electrical synapses play even in simple circuits. Because these canonical circuits are represented widely throughout the brain, we expect that these are general principles for the influence of electrical synapses on transient signal processing across the brain.Author SummaryThe role that electrical synapses play in neural oscillations, network synchronization and rhythmicity is well established, but their role neuronal processing of transient inputs is much less understood. Here we used computational models of canonical feedforward circuits and networks to investigate how the strength of electrical synapses regulates the flow of transient signals passing through those circuits. We show that because the influence of electrical synapses on coupled neighbors can be either inhibitory or excitatory, their role in network information processing is heterogeneous.. Because of the widespread existence of electrical synapses between interneurons as well as a growing body of evidence for their plasticity, we expect such effects play a significant role in how the brain processes transient inputs.

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A Computational Neuroscience Perspective on the Change Process in Psychotherapy

Neuroscience of Enduring Change ◽

10.1093/oso/9780190881511.003.0015 ◽

2020 ◽

pp. 395-432 ◽

Cited By ~ 2

Author(s):

Ryan Smith ◽

Richard D. Lane ◽

Lynn Nadel ◽

Michael Moutoussis

Keyword(s):

Computational Neuroscience ◽

Change Process ◽

Computational Models ◽

Therapeutic Process ◽

Repetitive Behavior ◽

Predictive Coding ◽

Emotional Awareness ◽

Limited Application ◽

The Brain

The application of computational neuroscience models to mental disorders has given rise to the emerging field of computational psychiatry. To date, however, there has been limited application of this approach to understanding the change process in psychotherapy. This chapter reviews leading approaches in computational neuroscience: predictive coding, active inference, and reinforcement learning. We then provide examples of how these complimentary approaches can be used to model a range of clinical phenomena and associated clinical interventions, including those associated with emotional awareness, specific phobia, maladaptive self-related beliefs, maladaptive repetitive behavior patterns, and the role of re-experiencing negative affect in the therapeutic process. The authors illustrate how this perspective can provide additional insights into the nature of the types of memories (cast as parameters in computational models) that maintain psychopathology, how they may be instantiated in the brain, and how new experiences in psychotherapy can alter/update these memories in a manner that can be quantitatively modeled. The authors conclude that the computational perspective represents a unique level of description that compliments that of the integrated memory model in a synergistic and informative manner.

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