scholarly journals NPY Released From GABA Neurons of the Dentate Gyrus Specially Reduces Contextual Fear Without Affecting Cued or Trace Fear

2021 ◽  
Vol 13 ◽  
Author(s):  
Lucas B. Comeras ◽  
Noa Hörmer ◽  
Pradeepa Mohan Bethuraj ◽  
Ramon O. Tasan
Keyword(s):  
Dentate Gyrus ◽  
Neuronal Excitability ◽  
Hippocampal Formation ◽  
Access Point ◽  
Severe Trauma ◽  
Ample Evidence ◽  
Contextual Fear ◽  
Gaba Neurons ◽  
Trace Fear ◽  
Somatostatin Neurons

Disproportionate, maladapted, and generalized fear are essential hallmarks of posttraumatic stress disorder (PTSD), which develops upon severe trauma in a subset of exposed individuals. Among the brain areas that are processing fear memories, the hippocampal formation exerts a central role linking emotional-affective with cognitive aspects. In the hippocampus, neuronal excitability is constrained by multiple GABAergic interneurons with highly specialized functions and an extensive repertoire of co-released neuromodulators. Neuropeptide Y (NPY) is one of these co-transmitters that significantly affects hippocampal signaling, with ample evidence supporting its fundamental role in emotional, cognitive, and metabolic circuitries. Here we investigated the role of NPY in relation to GABA, both released from the same interneurons of the dorsal dentate gyrus (DG), in different aspects of fear conditioning. We demonstrated that activation of dentate GABA neurons specifically during fear recall reduced cue-related as well as trace-related freezing behavior, whereas inhibition of the same neurons had no significant effects. Interestingly, concomitant overexpression of NPY in these neurons did not further modify fear recall, neither under baseline conditions nor upon chemogenetic stimulation. However, potentially increased co-release of NPY substantially reduced contextual fear, promoted extinction learning, and long-term suppression of fear in a foreground context–conditioning paradigm. Importantly, NPY in the dorsal DG was not only expressed in somatostatin neurons, but also in parvalbumin-positive basket cells and axoaxonic cells, indicating intense feedback and feedforward modulation of hippocampal signaling and precise curtailing of neuronal engrams. Thus, these findings suggest that co-release of NPY from specific interneuron populations of the dorsal DG modifies dedicated aspects of hippocampal processing by sharpening the activation of neural engrams and the consecutive fear response. Since inappropriate and generalized fear is the major impediment in the treatment of PTSD patients, the dentate NPY system may be a suitable access point to ameliorate PTSD symptoms and improve the inherent disease course.

Postnatal Development of the Hippocampus in Male Albino Rats: A Histomorphometric Study

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A A A Baraka ◽  
K A Hafez ◽  
A I A Othman ◽  
A M M Sadek
Keyword(s):  
Dentate Gyrus ◽  
Postnatal Development ◽  
Learning And Memory ◽  
Hippocampal Formation ◽  
Critical Role ◽  
Mammalian Brain ◽  
Albino Rats ◽  
Ammon's Horn ◽  
Hippocampus Proper ◽  
Ammon’S Horn

Abstract Introduction In recent year deterioration in cognitive, learning, and memory become one of the significant problems in human life. Hippocampus is a pivotal part of the brain’s limbic system which serves a critical role in memory, learning process and regulating the emotions. In most regions of the brain, neurons are generated only at specific periods of early development, and not born in the adulthood. In contrast, hippocampal neurons are generated throughout development and adult life. The hippocampal dentate gyrus was reported to be one of the few regions of the mammalian brain where neurogenesis continue to occur throughout adulthood. The neurogenesis in the dentate gyrus was thought to play an important role in hippocampus-dependent learning and memory. The hippocampal formation is composed of the hippocampus proper, the dentate gyrus and the subiculum. The hippocampus proper is the largest part and is subdivided into fields designated as Cornu Ammonis or Ammon’s horn (CA) from CA1 to CA4. Ammon's horn is continuous with the subiculum, which acts as the main output source of the hippocampal formation. Aim of the Study To study the postnatal development of the hippocampal formation. Materials and Methods Five male albino rats from the following postnatal ages day 1, week 1, week 2, week3 and week 4 were studied by histological, immunohistochemical, and morphometric methods. Results The general architecture of the hippocampus proper with its polymorphic, pyramidal, and molecular layers was present at day1, whereas the details of the adult structure appeared at week 2. In the dentate gyrus, distinct lamination appeared at week 1 and its maturation continued with the production of neurons at the interhilar zone that peaked at week 2. The number and density of pyramidal axons and dendrites increase by age. Astrocytes increased in size and staining affinity for glial filaments, and acquired a stellate shape with age. Furthermore, the number of granule cell layers increased concomitantly with the increase in thickness of the molecular and polymorphic layers of both the hippocampus proper and the dentate gyrus. Conclusion The important sequences of events in the growth and maturation of the hippocampal formation in male albino rat occurred in the first 2 postnatal weeks.

scholarly journals A STEREOLOGICAL ANALYSIS OF THE EFFECT OF EARLY POSTNATAL ETHANOL EXPOSURE ON NEURONAL NUMBERS IN RAT DENTATE GYRUS

2011 ◽  
Vol 19 (2) ◽  
pp. 99 ◽  
Author(s):  
Takanori Miki ◽  
Simon J Harris ◽  
Peter Wilce ◽  
Yoshiki Takeuchi ◽  
Kuldip S Bedi
Keyword(s):  
Dentate Gyrus ◽  
Hippocampal Formation ◽  
Ethanol Exposure ◽  
Learning Ability ◽  
Ethanol Ingestion ◽  
High Dose ◽  
Postnatal Life ◽  
Numerical Density ◽  
Rat Pups ◽  
Early Postnatal Life

Maternal ethanol ingestion during pregnancy can cause fetal alcohol syndrome (FAS) in their offspring. Among the symptoms of FAS, damage to the central nervous system has emerged as one of the most serious problems. We have previously shown that a relatively high dose of ethanol exposure during early postnatal life can cause alterations in spatial learning ability. This ability is controlled, at least in part, by the hippocampal formation. The purpose of the present study was to determine whether exposure of rat pups to ethanol during early postnatal life had effects on the total number of the dentate gyrus neurons. Wistar rats were exposed to a relatively high daily dose of ethanol between postnatal days 10 to 15. Ethanol exposure was achieved by placing rat pups in a chamber containing ethanol vapour for 3 hours a day. The blood ethanol concentration was found to be about 430 mg/dL at the end of the exposure period. Groups of ethanol treated (ET), separation controls (SC) and mother reared controls (MRC) were anaesthetised and killed at 16-days-of-age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volume of subdivisions of the dentate gyrus, and the physical disector method was used to estimate the numerical densities of neurons within each subdivision. The total number of neurons was calculated by multiplying estimates of the numerical density with the volume. There was, on average, about 421,000 granule cells in all three treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells. This value was significantly smaller than the average of 38,000 such neurons estimated to be present in both MRC and SC animals. It is concluded that neurons in the hilus region of the dentate gyrus may be particularly vulnerable to the effects of a high dose of ethanol exposure during PND 10-15. It is likely that this deficit was due to neuronal death induced by some mechanisms related to the ethanol exposure.

scholarly journals Transcription Factor 4 Safeguards Hippocampal Dentate Gyrus Development by Regulating Neural Progenitor Migration

2019 ◽  
Vol 30 (5) ◽  
pp. 3102-3115 ◽  
Author(s):  
Yafei Wang ◽  
Zhiheng Lu ◽  
Yilan Zhang ◽  
Yuqun Cai ◽  
Di Yun ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dentate Gyrus ◽  
Hippocampal Formation ◽  
Critical Role ◽  
Neural Progenitor ◽  
Downstream Effector ◽  
Severe Intellectual Disability ◽  
The Social ◽  
Developing Mouse Brain ◽  
Transcription Factor 4

Abstract The dentate gyrus (DG) of the hippocampal formation plays essential roles in learning and memory. Defective DG development is associated with neurological disorders. Here, we show that transcription factor 4 (Tcf4) is essential for DG development. Tcf4 expression is elevated in neural progenitors of the dentate neuroepithelium in the developing mouse brain. We demonstrate that conditional disruption of Tcf4 in the dentate neuroepithelium leads to abnormal neural progenitor migration guided by disorganized radial glial fibers, which further leads to hypoplasia in the DG. Moreover, we reveal that Wnt7b is a key downstream effector of Tcf4 in regulating neural progenitor migration. Behavioral analysis shows that disruption of integrity of the DG impairs the social memory highlighting the importance of proper development of the DG. These results reveal a critical role for Tcf4 in regulating DG development. As mutations in TCF4 cause Pitt–Hopkins syndrome (PTHS) characterized by severe intellectual disability, our data also potentially provide insights into the basis of neurological defects linked to TCF4 mutations.

Mossy Fiber–Granule Cell Synapses in the Normal and Epileptic Rat Dentate Gyrus Studied With Minimal Laser Photostimulation

1999 ◽  
Vol 82 (4) ◽  
pp. 1883-1894 ◽  
Author(s):  
Péter Molnár ◽  
J. Victor Nadler
Keyword(s):  
Status Epilepticus ◽  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Hippocampal Formation ◽  
Control Groups ◽  
Small Component ◽  
Fiber Growth ◽  
And Control

Dentate granule cells become synaptically interconnected in the hippocampus of persons with temporal lobe epilepsy, forming a recurrent mossy fiber pathway. This pathway may contribute to the development and propagation of seizures. The physiology of mossy fiber–granule cell synapses is difficult to characterize unambiguously, because electrical stimulation may activate other pathways and because there is a low probability of granule cell interconnection. These problems were addressed by the use of scanning laser photostimulation in slices of the caudal hippocampal formation. Glutamate was released from a caged precursor with highly focused ultraviolet light to evoke action potentials in a small population of granule cells. Excitatory synaptic currents were recorded in the presence of bicuculline. Minimal laser photostimulation evoked an apparently unitary excitatory postsynaptic current (EPSC) in 61% of granule cells from rats that had experienced pilocarpine-induced status epilepticus followed by recurrent mossy fiber growth. An EPSC was also evoked in 13–16% of granule cells from the control groups. EPSCs from status epilepticus and control groups had similar peak amplitudes (∼30 pA), 20–80% rise times (∼1.2 ms), decay time constants (∼10 ms), and half-widths (∼8 ms). The mean failure rate was high (∼70%) in both groups, and in both groups activation of N-methyl-d-aspartate receptors contributed a small component to the EPSC. The strong similarity between responses from the status epilepticus and control groups suggests that they resulted from activation of a similar synaptic population. No EPSC was recorded when the laser beam was focused in the dentate hilus, suggesting that indirect activation of hilar mossy cells contributed little, if at all, to these results. Recurrent mossy fiber growth increases the density of mossy fiber–granule cell synapses in the caudal dentate gyrus by perhaps sixfold, but the new synapses appear to operate very similarly to preexisting mossy fiber–granule cell synapses.

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