@article{2618ae4fd38f4bb0baa3ab48d1fabd20,
title = "Sub-circuit alterations in dorsal hippocampus structure and function after global neurodevelopmental insult",
abstract = "Patients with neuropsychiatric and neurological disorders often express limbic circuit abnormalities and deficits in information processing. While these disorders appear to have diverse etiologies, their common features suggest neurodevelopmental origins. Neurodevelopment is a prolonged process of diverse events including neurogenesis/apoptosis, axon pathfinding, synaptogenesis, and pruning, to name a few. The precise timing of the neurodevelopmental insult to these processes likely determines the resulting functional outcome. We used the epilepsy and schizophrenia-related gestational day 17 methylazoxymethanol acetate model to examine the impact of this timed neurodevelopmental insult on principal cell morphology and synaptic network function of the dorsal hippocampus (dHPC) circuit. Our observed structural and functional alterations in dHPC are compartment specific, indicating that adverse global exposure during gestation can produce specific alterations and distort information processing in neural circuits that underlie cognitive abilities.",
keywords = "Hippocampus, MAM, Morphology, Neurodevelopment, Physiology, Schizophrenia",
author = "O{\textquoteright}Reilly, {Kally C.} and Levy, {Eliott R.J.} and Patino, {Alejandra V.} and Perica, {Maria I.} and Fenton, {Andr{\'e} A.}",
note = "Funding Information: This work was supported by NIH-R01MH084038 and NIH-R25NS080686-06. The authors would like to thank Drs. Hsin-Yi Kao and Edith Lesburgueres for help generating control and GD17-MAM rats. We would also like to thank Yi-Wen Chen and Dr. Chiye Aoki for assistance with the Golgi studies. Preliminary reports of these data have been present at the Annual meetings for Society for Neuroscience (2016) and the Canadian Association for Neuroscience (2016). The authors have no conflicts to report. Funding Information: ◂Fig. 5 GD17-MAM rats have abnormal CA1 synaptic population responses to ventral hippocampal commissure stimulation. a Heat-maps of the average CSD in dHPC for control and GD17-MAM groups in response to ventral hippocampal commissure stimulation show spiking activity in CA1. For display purposes, the CSD was smoothed in the time direction. The gray dashed lines correspond to the time before and after the spiking activity that was quantified in b and c. Quantification of sinks and sources at maximum stimula-tion intensity within each layer of dHPC b before and c after spiking activity revealed no differences in sinks or sources in CA1 (pre-spike: sosink: t8 = 0.16, p = 0.87; pyrsource: t8 = 1.78, p = 0.11; str. rad.sink: t8 = 0.73, p = 0.48; Post-spike: sosink: t8 = 1.07, p = 0.31; pyrsource: t8 = 1.11, p = 0.30; str. rad.sink: t8 = 0.02, p = 0.99). Average CSD depth profiles (dark lines) and SEM (shaded) were created for (D) pyramidal layer and e str. rad at low intensity stimulation (100 µA) that did not elicit a population spike and high intensity stimulation (1000 µA) that did elicit a population spike. f The depth profiles were used to examine synaptic activity 1 ms before the population spike time that was elicited by the 1000 µA stimulation. There are no differences in synaptic activity in the pyramidal layer or str. rad at either stimulation intensity (pyr: 100µA: t8 = 0.15, p = 0.88; 1000 µA: t8 = 1.38, p = 0.20; str. rad : 100µA: t8 = 0.75, p = 0.47; 1000 µA: t12 = 1.17, p = 0.28). The fEPSP was quantified in g str. rad., where input fibers terminate, and h the pyramidal cell layer. There is no dif-ference in the slope of the fEPSP of CA1 at either the dendritic or cell layers (str. rad.: group: F1,8 = 0.88, p = 0.38, p = 0.37. stimula-tion intensity: F1.63,13.04 = 26.81, p = 0.0002; interaction: F1.63,13.04 = 0.11, p = 0.86; pyr: Group: F1,8 = 1.32, p = 0.28; stimulation intensity: F1.35,10.83 = 14.36, p = 0.004; interaction: F1.35,10.83 = 1.73, p=0.22). j The population spiking activity was measured at the cell layer. The CA1 population spike response to ventral hippocampal commissure stimulation is indistinguishable between GD17-MAM and control rats (group: F1,8 = 3.21, p = 0.11; stimulation intensity: F1.80,14.35 = 9.30, p = 0.009; interaction: F1.80,14.35 = 2.38, p=0.15). Calibration is the same in g, h, and j. The multivariate relationships between k fEPSP slope at the dendrite (str. rad.) and fEPSP slope at the soma (pyramidal layer) and l the fEPSP slope at the dendrite (str. rad.) and the population spiking activity at the soma (pyramidal layer) are attenuated in GD17-MAM rats and there is a significant difference between cumulative probabilities (h control n = 160, GD17-MAM n = 240, Mann–Whitney U = 5.3 × 103, p = 10−15; j Mann–Whitney U = 1.04 × 104, p = 10−15). Values are average ± SEM, except in k and l, where each individual value is plotted. control n = 4, GD17-MAM n = 6. so = stratum oriens, pyr = pyramidal layer, str. rad. = stratum radiatum, slm = stratum lacunosum moleculare, mol = molecular layer of DG, grc = granule cell layer of DG Acknowledgements This work was supported by NIH-R01MH084038 and NIH-R25NS080686-06. The authors would like to thank Drs. Hsin-Yi Kao and Edith Lesburgueres for help generating control and GD17-MAM rats. We would also like to thank Yi-Wen Chen and Dr. Chiye Aoki for assistance with the Golgi studies. Preliminary reports of these data have been present at the Annual meetings for Society for Neuroscience (2016) and the Canadian Association for Neuroscience (2016). Publisher Copyright: {\textcopyright} 2018, Springer-Verlag GmbH Germany, part of Springer Nature.",
year = "2018",
month = nov,
day = "1",
doi = "10.1007/s00429-018-1704-3",
language = "English (US)",
volume = "223",
pages = "3543--3556",
journal = "Brain Structure and Function",
issn = "1863-2653",
publisher = "Springer Verlag",
number = "8",
}