scholarly journals Increased Excitability and Heightened Magnitude of Long-Term Potentiation at Hippocampal CA3–CA1 Synapses in a Mouse Model of Neonatal Hyperoxia Exposure

2021 ◽  
Vol 12 ◽  
Author(s):  
Manimaran Ramani ◽  
Kiara Miller ◽  
Namasivayam Ambalavanan ◽  
Lori L. McMahon
Keyword(s):  
Learning And Memory ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Spatial Learning And Memory ◽  
Normobaric Oxygen ◽  
Hyperoxia Exposure ◽  
Hippocampal Ca3 ◽  
Neonatal Hyperoxia

Preterm infants exposed to supraphysiological oxygen (hyperoxia) during the neonatal period have hippocampal atrophy and cognitive dysfunction later in childhood and as adolescents. Previously, we reported that 14-week-old adult mice exposed to hyperoxia as newborns had spatial memory deficits and hippocampal shrinkage, findings that mirror those of human adolescents who were born preterm. The area CA1 region of the hippocampus that is crucial for spatial learning and memory is highly vulnerable to oxidative stress. In this study, we investigated the long-term impact of neonatal hyperoxia exposure on hippocampal CA3–CA1 synaptic function. Male and female C57BL/6J mouse pups were continuously exposed to either 85% normobaric oxygen or air between postnatal days 2–14. Hippocampal slice electrophysiology at CA3–CA1 synapses was then performed at 14 weeks of age. We observed that hyperoxia exposed mice have heightened strength of basal synaptic transmission measured in input-output curves, increased fiber volley amplitude indicating increased axonal excitability, and heightened LTP magnitude at CA3–CA1 synapses, likely a consequence of increased postsynaptic depolarization during tetanus. These data demonstrate that supraphysiological oxygen exposure during the critical neonatal developmental period leads to pathologically heightened CA3–CA1 synaptic function during early adulthood which may contribute to hippocampal shrinkage and learning and memory deficits we previously reported. Furthermore, these results will help shed light on the consequences of hyperoxia exposure on the development of hippocampal synaptic circuit abnormalities that could be contributing to cognitive deficits in children born preterm.

scholarly journals Increased Excitability and Heightened Magnitude of Long-term Potentiation at Hippocampal CA3-CA1 Synapses in a Mouse Model of Neonatal Hyperoxia Exposure

2020 ◽  
Author(s):  
Manimaran Ramani ◽  
Kiara Miller ◽  
Namasivayam Ambalavanan ◽  
Lori L McMahon
Keyword(s):  
Learning And Memory ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Spatial Learning And Memory ◽  
Normobaric Oxygen ◽  
Hyperoxia Exposure ◽  
Hippocampal Ca3 ◽  
Neonatal Hyperoxia

AbstractPreterm infants exposed to supraphysiological oxygen (hyperoxia) during the neonatal period have hippocampal atrophy and cognitive dysfunction later in childhood and as adolescents. Previously, we reported that 14-week-old adult mice exposed to hyperoxia as newborns had spatial memory deficits and hippocampal shrinkage, findings that mirror those of adolescents who were born preterm. Area CA1 region of the hippocampus that is crucial for spatial learning and memory is highly vulnerable to oxidative stress. In this study, we investigated the long-term impact of neonatal hyperoxia exposure on hippocampal CA3-CA1 synaptic function. Male and female C57BL/6J mouse pups were continuously exposed to either 85% normobaric oxygen or air between postnatal days 2-14. Hippocampal slice electrophysiology at CA3-CA1 synapses was then performed at 14 weeks of age. We observed that hyperoxia exposed mice have heightened strength of basal synaptic transmission measured in input-output curves, increased fiber volley amplitude indicating increased axonal excitability, and heightened LTP magnitude at CA3-CA1 synapses, likely a consequence of increased postsynaptic depolarization during the tetanus. These data demonstrate that supraphysiological oxygen exposure during the critical neonatal developmental period leads to pathologically heightened CA3-CA1 synaptic function during early adulthood which may contribute to hippocampal shrinkage and learning and memory deficits we previously reported. Furthermore, these changes may account for cognitive disorders in children born preterm who were exposed to prolonged oxygen supplementation.

scholarly journals CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Miou Zhou ◽  
Stuart Greenhill ◽  
Shan Huang ◽  
Tawnie K Silva ◽  
Yoshitake Sano ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Cognitive Deficits ◽  
Barrel Cortex ◽  
Cortical Plasticity ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Dependent Plasticity ◽  
Term Potentiation

Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.

scholarly journals Layer 2/3 Synapses in Monocular and Binocular Regions of Tree Shrew Visual Cortex Express mAChR-Dependent Long-Term Depression and Long-Term Potentiation

2008 ◽  
Vol 100 (1) ◽  
pp. 336-345 ◽  
Author(s):  
Portia McCoy ◽  
Thomas T. Norton ◽  
Lori L. McMahon
Keyword(s):  
Visual Cortex ◽  
Learning And Memory ◽  
Tree Shrew ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Muscarinic Acetylcholine Receptors ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Layer 2

Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

scholarly journals Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Samaneh Safari ◽  
Nesa Ahmadi ◽  
Reihaneh Mohammadkhani ◽  
Reza Ghahremani ◽  
Maryam Khajvand-Abedeni ◽  
...  
Keyword(s):  
Sex Differences ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Female Rats ◽  
Male Rats ◽  
Spatial Learning And Memory ◽  
Term Potentiation

Abstract Background Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. Results In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. Conclusions Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.

scholarly journals Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to long-term potentiation and spatial learning

2016 ◽  
Vol 113 (46) ◽  
pp. 13209-13214 ◽  
Author(s):  
Evanthia Nanou ◽  
Todd Scheuer ◽  
William A. Catterall
Keyword(s):  
Synaptic Plasticity ◽  
Glutamate Receptors ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Spatial Learning And Memory ◽  
Calcium Sensor ◽  
Short Term ◽  
Sensor Proteins

Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca2+ type 2.1 (CaV2.1) channels. However, the contribution of regulation of CaV2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of CaV2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically. LTP in response to θ-burst stimulation and to 100-Hz tetanic stimulation is much reduced. However, a normal level of LTP can be generated by repetitive 100-Hz stimulation or by depolarization of the postsynaptic cell to prevent block of NMDA-specific glutamate receptors by Mg2+. The ratio of postsynaptic responses of NMDA-specific glutamate receptors to those of AMPA-specific glutamate receptors is decreased, but the postsynaptic current from activation of NMDA-specific glutamate receptors is progressively increased during trains of stimuli and exceeds WT by the end of 1-s trains. Strikingly, these impairments in long-term synaptic plasticity and the previously documented impairments in short-term synaptic plasticity in IM-AA mice are associated with pronounced deficits in spatial learning and memory in context-dependent fear conditioning and in the Barnes circular maze. Thus, regulation of CaV2.1 channels by calcium sensor proteins is required for normal short-term synaptic plasticity, LTP, and spatial learning and memory in mice.

Sign in / Sign up

Export Citation Format

Share Document