scholarly journals Melamine Disrupts Acetylcholine-Mediated Neural Information Flow in the Hippocampal CA3–CA1 Pathway

2021 ◽  
Vol 15 ◽  
Author(s):  
Wei Sun ◽  
Peidong Liu ◽  
Chunzhi Tang ◽  
Lei An
Keyword(s):  
Information Flow ◽  
Spatial Learning ◽  
Phase Synchronization ◽  
Field Potential ◽  
Treated Group ◽  
Intragastric Administration ◽  
Learning Deficits ◽  
Y Maze ◽  
Neural Information ◽  
Hippocampal Ca3

Considering the cognitive and synaptic deficits following intragastric administration of melamine, the aim of the current investigation was to test whether the hippocampal oscillations were affected. The local field potential (LFP) was recorded in the hippocampal CA3–CA1 pathway of Wistar rats during a spatial-dependent Y-maze task. The general partial directed coherence (gPDC) method was used to assess the directionality of neural information flow (NIF) between the CA3 and CA1 regions. The levels of acetylcholine (ACh) and its esterolytic protease, acetylcholinesterase (AChE), were detected in the hippocampus (HPC) following the behavioral test. The values of phase synchronization between the CA3 and CA1 regions in delta, low theta, and high theta oscillations were reduced significantly in the melamine-treated group. Moreover, the coupling directional index and the strength of CA3 driving CA1 were critically decreased in the above three frequency bands as well. Meanwhile, a reduction in ACh expression and an enhancement in AChE activity were found in the HPC of melamine-treated rats. Intrahippocampal infusion with ACh could mitigate the weakened neural coupling and directional NIF in parallel with spatial learning improvements. However, infusion of scopolamine, an acetylcholine receptor antagonist, could block the mitigative effects of ACh treatment in melamine rats. These findings provide first evidence that ACh-mediated neuronal coupling and NIF in the CA3–CA1 pathway are involved in spatial learning deficits induced by chronic melamine exposure.

Subacute melamine exposure disrupts task-based hippocampal information flow via inhibiting the subunits 2 and 3 of AMPA glutamate receptors expression

2020 ◽  
pp. 096032712097582
Author(s):  
Wei Sun ◽  
Xiaoliang Li ◽  
Dongxin Tang ◽  
Yuanhua Wu ◽  
Lei An
Keyword(s):  
Information Flow ◽  
Spatial Learning ◽  
Phase Synchronization ◽  
Neural Function ◽  
Learning Deficits ◽  
Postsynaptic Receptors ◽  
Ca1 Region ◽  
Hippocampal Ca1 ◽  
Neural Information ◽  
Hippocampal Ca3

Although melamine exposure induces cognitive deficits and dysfunctional neurotransmission in hippocampal Cornus Ammonis (CA) 1 region of rats, it is unclear whether the neural function, such as neural oscillations between hippocampal CA3–CA1 pathway and postsynaptic receptors involves in these effects. The levels of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit glutamate receptor (GluR) 1 and GluR2/3 in CA1 region of melamine-treated rats, which were intragastric treated with 300 mg/kg/day for 4 weeks, were detected. Following systemic or intra-hippocampal CA1 injection with GluR2/3 agonist, spatial learning of melamine-treated rats was assessed in Morris water maze (MWM) task. Local field potentials were recorded in CA3–CA1 pathway before and during behavioral test. General Partial Directed Coherence approach was applied to determine directionality of neural information flow between CA3 and CA1 regions. Results showed that melamine exposure reduced GluR2/3 but not GluR1 level and systemic or intra-hippocampal CA1 injection with GluR2/3 agonist effectively mitigated the learning deficits. Phase synchronization between CA3 and CA1 regions were significantly diminished in delta, theta and alpha oscillations. Coupling directional index and strength of CA3 driving CA1 were marked reduced as well. Intra-hippocampal CA1 infusion with GluR2/3 agonist significantly enhanced the phase locked value and reversed the melamine-induced reduction in the neural information flow (NIF) from CA3 to CA1 region. These findings support that melamine exposure decrease the expression of GluR2/3 subunit involved in weakening directionality index of NIF, and thereby induced spatial learning deficits.

scholarly journals In silico hippocampal modeling for multi-target pharmacotherapy in schizophrenia

2019 ◽  
Author(s):  
Mohamed A Sherif ◽  
Samuel A Neymotin ◽  
William W Lytton
Keyword(s):  
Information Processing ◽  
Information Flow ◽  
Target Therapy ◽  
Field Potential ◽  
Intermediate Level ◽  
Gamma Activity ◽  
Cognitive Symptoms ◽  
Potential Biomarker ◽  
Gamma Power ◽  
Hippocampal Ca3

AbstractBackgroundTreatment of schizophrenia has had limited success in treating core cognitive symptoms. The evidence of multi-gene involvement suggests that multi-target therapy may be needed. Meanwhile, the complexity of schizophrenia pathophysiology and psychopathology, coupled with the species-specificity of much of the symptomatology, places limits on analysis via animal models, in vitro assays, and patient assessment. Multiscale computer modeling complements these traditional modes of study.MethodsUsing a hippocampal CA3 computer model with 1200 neurons, we examined the effects of alterations in NMDAR, HCN (Ih current), and GABAAR on information flow (measured with normalized transfer entropy), and in gamma activity in local field potential (LFP).ResultsAltering NMDARs, GABAAR, Ih, individually or in combination, modified information flow in an inverted-U shape manner, with information flow reduced at low and high levels of these parameters. The strong information flow seen at the peaks were associated with an intermediate level of synchrony, seen as an intermediate level of gamma activity in the LFP, and an intermediate level of pyramidal cell excitability.ConclusionsOur results are consistent with the idea that overly low or high gamma power is associated with pathological information flow and information processing. These data suggest the need for careful titration of schizophrenia pharmacotherapy to avoid extremes that alter information flow in different ways. These results also identify gamma power as a potential biomarker for monitoring pathology and multi-target pharmacotherapy.AUTHOR SUMMARYCurrently, there are no good treatments for the cognitive symptoms of schizophrenia. We used a biophysically realistic computational model of hippocampal CA3 to investigate the effect of potential pharmacotherapeutic targets on the dynamics of CA3 activity and information processing to predict multi-target drug treatments for schizophrenia. We found an inverted-U shaped relationship between information flow and drug target manipulations, as well as between information flow and gamma power. Our study suggests that neuronal excitability and synchrony may be tuned between extremes to enhance information flow and information processing. It further predicts the need for careful titration of schizophrenia drugs, whether used individually or in drug cocktails.

Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mahmoud Hashemzaei ◽  
Najmeh Baratzadeh ◽  
Iraj Sharamian ◽  
Sahar Fanoudi ◽  
Mehdi Sanati ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Spatial Memory ◽  
Morris Water Maze ◽  
Spatial Learning ◽  
Water Maze ◽  
Synergistic Effects ◽  
Deionized Water ◽  
Learning Deficits ◽  
Learning Impairments ◽  
Morris Water Maze Task

Abstract Objectives H-89 (a protein kinase AII [PKA II] inhibitor) impairs the spatial memory in the Morris water maze task in rats. In the present study, we aimed to study the protective effects of nicotine and O-acetyl-L-carnitine against H-89-induced spatial memory deficits. Methods Spatial memory impairment was induced by the bilateral intrahippocampal administration of 10 µM H-89 (dissolved in dimethyl sulfoxide, DMSO) to rats. The rats then received bilateral administrations of either nicotine (1 μg/μL, dissolved in saline) or O-acetyl-L-carnitine (100 μM/side, dissolved in deionized water) alone and in combination. Control groups received either saline, deionized water, or DMSO. Results The H-89-treated animals showed significant increases in the time and distance travelled to find hidden platforms, and there was also a significant decrease in the time spent in the target quadrant compared to DMSO-treated animals. Nicotine and O-acetyl-L-carnitine had no significant effects on H-89-induced spatial learning impairments alone, but the bilateral intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevented H-89-induced spatial learning deficits and increased the time spent in the target quadrant in comparison with H-89-treated animals. Conclusions Our results indicated the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.

Spatial Learning Deficits in Preschool Children of Alcoholics

1995 ◽  
Vol 19 (4) ◽  
pp. 1067-1072 ◽  
Author(s):  
Steven L. Schandler ◽  
Connie S. Thomas ◽  
Michael J. Cohen
Keyword(s):  
Preschool Children ◽  
Spatial Learning ◽  
Children Of Alcoholics ◽  
Learning Deficits

Mice lacking hippocampal left-right asymmetry show non-spatial learning deficits

2018 ◽  
Vol 336 ◽  
pp. 156-165 ◽  
Author(s):  
Akihiro Shimbo ◽  
Yutaka Kosaki ◽  
Isao Ito ◽  
Shigeru Watanabe
Keyword(s):  
Spatial Learning ◽  
Learning Deficits ◽  
Left Right Asymmetry

Age-related psychomotor and spatial learning deficits in 129/SvJ mice

1999 ◽  
Vol 20 (1) ◽  
pp. 9-18 ◽  
Author(s):  
John M Hengemihle ◽  
Jeffrey M Long ◽  
Jennifer Betkey ◽  
Mathias Jucker ◽  
Donald K Ingram
Keyword(s):  
Spatial Learning ◽  
Learning Deficits ◽  
Age Related

scholarly journals Spatial learning deficits following traumatic brain injury in rats: Reversal by bFGF

1998 ◽  
Vol 76 ◽  
pp. 193
Author(s):  
Hiroshi Uramoto ◽  
Shizuo Nakamura ◽  
Kyoshi Saitoh ◽  
Tomochika Ohno
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spatial Learning ◽  
Learning Deficits

The dendritic origins of penicillin-induced epileptogenesis in CA3 hippocampal pyramidal cells

1986 ◽  
Vol 56 (6) ◽  
pp. 1718-1738 ◽  
Author(s):  
J. W. Swann ◽  
R. J. Brady ◽  
R. J. Friedman ◽  
E. J. Smith
Keyword(s):  
Cell Body ◽  
Average Distance ◽  
Hippocampal Slices ◽  
Current Source ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Large Current ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Cells ◽  
Negative Field

Experiments were performed in order to identify the sites of epileptiform burst generation in rat hippocampal CA3 pyramidal cells. A subsequent slow field potential was studied, which is associated with afterdischarge generation. Laminar field potential and current source-density (CSD) methods were employed in hippocampal slices exposed to penicillin. Simultaneous intracellular and extracellular field recordings from the CA3 pyramidal cell body layer showed that whenever an epileptiform burst was recorded extracellularly, individual CA3 neurons underwent an intense depolarization shift. In extracellular records a slow negative field potential invariably followed epileptiform burst generation. In approximately 10% of slices, synchronous afterdischarges rode on the envelope of this negative field potential. Intracellularly a depolarizing afterpotential followed the depolarization shift and was coincident with the extracellular slow negative field potential. A one-dimensional CSD analysis performed perpendicular to the CA3 cell body layer showed that during epileptiform burst generation large current sinks occur simultaneously in the central portions of both the apical and basilar dendrites. The average distance of the peak amplitude for these sinks from the center of the cell body layer was 175 +/- 46.8 microns and 158 +/- 25.0 microns, respectively. A large current source was recorded in the cell body layer. Smaller current sources were observed in the distal portions of the dendritic layers. During the postburst slow field potential a current sink was recorded at the edge of the cell body layer in stratum oriens--a region referred to as the infrapyramidal zone. Simultaneous with the current sink recorded there, smaller sinks were often observed in the dendritic layers that appeared to be "tails" or prolongations of the currents underlying burst generation. Two-dimensional analyses of these field potentials were performed on planes parallel and perpendicular to the exposed surface of the slice. Isopotential contours showed that the direction of extracellular current is mainly orthogonal to the CA3 laminae. Correction of CSD estimates made perpendicular to the cell body layer for current flowing in the other direction did not alter the location of computed current sources and sinks. In order to show that the dendritic currents associated with epileptiform burst generation were active sinks, tetrodotoxin (TTX) was applied locally to the dendrites where the current sinks were recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

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