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/lp/springer-journals/sex-differences-in-spatial-learning-and-memory-and-hippocampal-long-PyAQHHTh0A
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- Springer Journals
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- Copyright © The Author(s) 2021
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- 1744-9081
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- 10.1186/s12993-021-00184-y
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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 poten‑ tials (fEPSP) slope. Conclusions: Taken together, our results suggest that sex differences in the LTP at PP ‑DG synapses, possibly contrib ‑ ute to the observed sex difference in spatial learning and memory. Keywords: Long‑term potentiation, Hippocampus, Dentate Gyrus, Spatial learning and memory, Sex difference, Wistar Rat Background to have different strategies for decision-making and Male and female nervous system respond differently to memory encoding. Because the nervous system controls abnormal physiological situations [1], so finding sex dif - cognitive behaviour, these sex-related functional differ - ferences in diverse brain functions seems essential. Stud- ences may be associated to the sex-specific structure of ies have shown that gender may have a substantial effect the neuronal circuits in the nervous system [3]. on human cognitive ability [2]. Men and women appear Spatial memory is responsible for spatial orientation and retrieving information about the locations of objects and places in the environment [4]. Gender differences in *Correspondence: asad_karimi_128@yahoo.com; a.karimi@umsha.ac.ir; cognition have been described in cognitive and behav- asadkarimi@sbmu.ac.ir ioral psychology for many years [5]. Moreover, several Samaneh Safari and Nesa Ahmadi contributed equally to this work studies have reported sex differences in spatial ability in Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran humans, primates, and rodents [4, 6–10]. Overall, males Full list of author information is available at the end of the article © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom‑ mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Safari et al. Behav Brain Funct (2021) 17:9 Page 2 of 11 excel in spatial processing, while females excel in verbal Results work [11–14]. Also. studies on rodents and humans have Behavior shown that males have better performance on spatial Memory acquisition in MWM memory tasks to females [4, 15–17]. The time to locate the hidden platform or swim distance On the other hand, some groups claim that there is in training days decreased in both male and female rats. no gender difference in spatial memory ability [18–20]. This means that the performance of animals improved According to the literature, the results seem to be varied during the 4-day training period. Figure 1 shows the data and divisive, from ‘‘substantial difference” to ‘‘no signifi - for the swimming distance to find the hidden platform. cant difference”. In the current work, we first attempted There was a significant main effect of training day on to determine sex differences in spatial memory and swim distance [F (1.623, 22.72) = 56.59, P < 0.0001]. In sought to find possible underlying mechanisms in rats. general, male rats had shorter swimming paths to escape Some works have shown that the brain areas related onto the hidden platform (P < 0.05), indicating that males with spatial anility can be different in each sex or have had better performance than females. Escape latency to different functions [21–25]. Nevertheless, the main neu - find hidden platform (Fig. 2.) increased in female animals ral circuits and underlying mechanisms responsible for when compared with male rats. There was a significant these differences are not fully understood and there are main effect of training day on escape latency [F (2.562, contradictions in this regard. 35.87) = 23.22, P < 0.0001]. Overall, male rats had shorter There is much evidence that the hippocampus plays an escape latency to find the hidden platform, indicating important role for long-term memory and is necessary that males had better performance than females. for episodic and spatial memory [26–28]. The hippocam - pus shows high degree of synaptic plasticity. Two main Probe trial performance in MWM classes of synaptic plasticity are long-term potentiation The probe test was performed 24 h after the last training (LTP) and long-term depression (LTD). It is well well- trial test on day 5 to assess the reference memory. Dur- known that hippocampal LTP is the essential mechanism ing this test, the platform was removed and swimming for spatial memory [29, 30]. On the other hand, due to speed, time spent and distance traveled in target zone the main role of LTP in memory, differences in the induc - of the MWM were recorded. These data are shown in tion or expression of LTP between males and females Fig. 3. Female rats spent less time in the target zone in may be the cause of gender differences in spatial memory. compare with male animals (female rats: 13.83 ± 2.04 s , There is controversy about sex differences in synap - male: 20.35 ± 1.03 s, (t = 3.03, P = 0.025, Fig . 3a). tic plasticity. Strong sex differences in LTP induction Female rats traveled less distance in the target zone have been reported in dentate gyrus (DG) of pentobar- bital and/or urethane-anesthetized rats [31, 32] and also in CA1 region of hippocampal slices [33–35]. However, some studies have reported no difference in LTP at the Male perforant pathway (PP)-DG synapses [36, 37]. It has been Female reported that the LTP magnitude is not different depend - ing on the sex [35, 37]. Stephen et al. have reported sex 2000 differences in hippocampal LTP, but their results showed that, unlike sex difference in field excitatory post syn - aptic potentials (fEPSP) slope LTP, a sex difference in population spike (PS) amplitude LTP was not apparent [32]. Monfort et al. have also shown that hippocampal LTP in the CA1 region is reduced in mature compared to young male rats but not in female rats [38]. In our opin- Day 1Day 2Day 3Day 4 ion, these findings should be repeated because there is no consistency in the literature about sex differences in Training Days cognitive functions such as spatial learning and memory Fig. 1 Swim traveled to find the hidden platform during training and LTP. Therefore, the aim of the current work was to days. Each point represents the daily average of each group. evaluate whether is there a difference between male and Performance of all animals improved during the 4‑ day training female rats in spatial learning and memory in the Mor- period. Swim distance in training days decreased in both male and ris water maze (MWM)? And whether changes in spatial female rats. Male rats had shorter swimming paths to escape onto the learning and memory are related to hippocampal LTP at hidden platform than female rats. Data presented as mean ± S.E.M. *p < 0.05 PP-DG synapses. SwimDistance(Cm) S afari et al. Behav Brain Funct (2021) 17:9 Page 3 of 11 visible platform during visible experiment were the Male same in male and female rats (Fig. 4, P > 0.05). Female LTP at PP‑DG synapses We studied LTP at PP-DG synapses in urethane-anes- thetized rats to evaluate sex differences in hippocampal synaptic plasticity. Male and female rats were tested for probable differences in PP-DG LTP induction. Before and after high frequency stimulation in PP, the extracellular field potentials were recorded in the DG area. LTP was determined by examining HFS-induced changes in the fEPSP slope and PS amplitude. Representative traces of Day 1Day 2Day 3Day 4 LTP recording are shown in the upper panel of Fig. 5. Excitatory postsynaptic potential LTP Training Days As shown in Fig. 5, the magnitude of fEPSP slope LTP Fig. 2 Latency to find a hidden platform during training days. Each varied with sex of the rats. Two-way repeated-measures point represents the daily average of each group. Performance of all animals improved during the 4‑ day training period. The time to locate ANOVA revealed significant effect of time- points [F the hidden platform decreased in both male and female rats. Male (1.393, 15.32) = 15.05, P = 0.0006], significant effect of sex rats had less latency to escape onto the hidden platform than female [F (1, 11) = 5.921, P = 0.0332], and a significant interac - rats. Data presented as mean ± S.E.M. *p < 0.05 tion of the two [F (3, 33) = 4.869, P = 0.0065] in slope of fEPSP of the granular cell of DG (Fig. 5). Post-hoc com- parisons (P < 0.05) indicated that males exhibited sig- in compare with male animals (t = 2.38, P = 0.03, nificantly more fEPSP slope LTP than female rats. The Fig. 3b). Considering that in the probe test, the swim- percentage change in fEPSP slope after HFS was signifi - ming speed was the same in male and female animals, cantly lower in female rats than in male rats. it can be concluded that there are no motor disorders in these animals (t = 0.6369, P = 0.5361, Fig . 3b). In Population spike LTP the visible experiment that took place after the probe The sex difference in PS amplitude LTP was also evident, test, all the animals were able to find the platform. The as shown in Fig. 6. Two-way repeated-measures ANOVA results showed that there was no visual impairment revealed significant effect of time- points [F (1.393, in the animals because the escape latencies to find the 15.32) = 15.05, P = 0.0006], significant effect of sex [F (1, 11) = 5.921, P = 0.0332], and a significant interaction (c) (b) (a) Male Female Male Female Male Female Fig. 3 Probe trial performance of male and female rats. Female rats spent less time a and traveled less distance b in the target zone. Swimming speed was same in both male and female animals (c). Data presented as mean ± S.E.M. *p < 0.05 Escape Latency(Sec) Time SpentinTargetZone(Sec) Distance traveledintargetzone(cm) Swimming Speed(cm/sec) Safari et al. Behav Brain Funct (2021) 17:9 Page 4 of 11 of the two [F (3, 33) = 4.869, P = 0.0065] in amplitude of PS in the granular cell of DG (Fig. 6). Post-hoc compari- sons (P < 0.0001) indicated that male rats exhibited sig- nificantly more PS amplitude LTP than female rats. The percentage change in PS amplitude after HFS was signifi - cantly lower in female rats than in male rats. Discussion The present study investigated sex differences in spatial 0 ability and synaptic plasticity. Overall, male rats had a Male Female better performance than female rats in MWM task. Sex Fig. 4 Latency to escape onto the visible platform during visible differences in LTP were also evident in the PS amplitude experiment. There was no visual impairment in the animals because and the slope of fEPSP at PP-DG synapses. Male rats the escape latencies to find the visible platform during visible exhibited significantly more PS amplitude and fEPSP experiment were the same in male and female rats. Data presented slope than female rats. Our data in the current work, as mean ± S.E.M using Wistar rats, are consistent with most other works showing that male rats had a better performance than female rats in MWM task. There is controversy about sex differences in synaptic plasticity. For example, sex differences in LTP induction After HFS After HFS Before HFS Before HFS Male Female Male Female Male Female Base LTP 5LTP 30 LTP 60 Fig. 5 Time‑ dependent variations in hippocampal evoked responses to PP stimulation following an HFS. Upper panel shows representative traces of evoked field potential recording in the DG area prior to and 60 min after HFS. Male rats exhibited significantly more fEPSP slope LTP than females. Left lower panel shows fEPSP slope change (%) vs. time following HFS in both sex of rats. Bar graphs show the average fEPSP slope change (%) during 60 min post‑HFS. Data are expressed as means ± SEM % of baseline. *P < 0.05 Escape latencytofind thevisible platform (Sec) EPSP slope(%ofBaseline) Potentiation (%) S afari et al. Behav Brain Funct (2021) 17:9 Page 5 of 11 Male Female 600 300 **** Male Female Base LTP 5LTP 30 LTP 60 Fig. 6 Time‑ dependent variations in hippocampal evoked responses to PP stimulation following an HFS. Male rats exhibited significantly more PS amplitude LTP than females. Left panel shows PS amplitude change (%) vs. time following HFS in both sex of rats. Bar graphs show the average PS amplitude change (%) during 60 min post‑HFS. Data are expressed as means ± SEM % of baseline. *P < 0.0001 have been reported in DG [31, 32] and in CA1 [33–35]. claimed that this effect is specific to females [50]. Modu - Furthermore, it has been reported that the LTP magni- lation of synaptic plasticity by estrogens may be respon- tude is not different between males and females [35, 37]. sible for sex differences in synaptic plasticity and lower Also, study by Chen et al. Showed that amygdala LTP is LTP in female rats. In males, overexpression of NMDA 2+ higher in female mice than male mice [39]. On the other receptors may lead to higher Ca entry and facilitate hand, it has been reported that there is no sex difference LTP induction [51]. NMDA receptors play a main role in for LTP in the amygdala [40]. These different observation both LTP and spatial learning and memory [52–54]. on sex differences in synaptic plasticity may be due to dif - It has also been reported that changes in the number of ferent LTP recording protocols or recording in different AMPA receptors, their subunit composition, and phos- brain areas. phorylation state can alter synaptic plasticity [55]. AMPA An important difference in spatial learning and mem - receptor function and trafficking play an important role ory between male and female rats appears to be that they in LTP. In females, lower trafficking of AMPA receptors use different learning approaches that are controlled by in the synaptic membrane may be responsible for lower different areas of the brain. The preference of adult male LTP [34]. The lower trafficking and insertion of AMPA rats is a hippocampal-dependent spatial strategy rather receptors is due to lower activation of cGMP-dependent than a striatum-dependent response strategy. In con- protein kinase (PKG) [34]. PKG inhibition prevents the trast, female rats prefer a spatial strategy only when the insertion of AMPA receptors into membranes, resulting concentration of estradiol in their bloodstream increases in a decrease in hippocampal LTP [56]. [41]. One of the reasons for the low ability of females in spa- Sex differences in hippocampal-related behaviors sug - tial learning and memory is lower magnitude of LTP in gest that there may be differences in the organization females, and mechanisms that reduce LTP may also be and function of hippocampal neural circuits in males and involved in low performance of females in MWM task. females. Some studies have reported that the male hip- Because both LTP and spatial learning are disrupted by pocampus is larger than women [42, 43], although other inhibition of NMDA receptors [57, 58]. Impairment in studies have not shown such results [44–47]. LTP and impaired spatial learning and working mem- Female rats display a reduced hippocampal LTP com- ory have also been reported in mice lacking the GluR-A pared to males. These changes may be related to the (GluR1) AMPA receptor subunit [59]. modulation of glutamatergic synaptic transmission and Also, sex differences in spatial ability appear to be in particular the function of N-methyl-D-aspartic acid related to stress [60]. And female performance in the (NMDA) receptors and synaptic plasticity by estrogens MWM may be more sensitive to stress. No sex differ - [48–50]. Estradiol has been shown to affect synaptogen - ences in spatial performance were observed when the esis and dendritic spine density in the hippocampus in rats were pre-exposed to the environment [61, 62]. Pre- female mice. Males treated with estradiol did not show exposure of animals to the MWM apparatus and testing an increase in hippocampal spine density, so it can be procedures before hidden platform training has been PS Amplitude(%ofbaseline) Potentiation (%) Safari et al. Behav Brain Funct (2021) 17:9 Page 6 of 11 shown to reduce or eliminate sex differences in MWM levels may be limitations of the present study, which performance and response to stress. Pre-exposure to should be considered in future studies. MWM apparatus and testing procedures reduces stress and stress-related hormones (e.g. corticosterone) during the test, and females may have better performance in less Methods stressful situations [63, 64]. It has also been shown that Animals and ethics statement reversing the stress response by performing an adrenal- In the present study, 2-month-old male and female ectomy eliminates sex difference in MWM performance Wistar rats were used. A total of 15 male (8 for MWM [63]. and 7 for electrophysiology) and 15 female (8 for MWM Higher thigmotaxis levels in the MWM test in females and 7 for electrophysiology) rats were used. The housing could be another cause of sex differences in spatial ability conditions of rats were as follows: Room temperature: [62, 63, 65, 66]. Also, it has been shown that after MWM 22 ± 2 °C; Light–dark cycles: (12 h light‐12 h dark); The test, the level of thigmotaxis is positively associated with number of rats per cage: 2–3 rats; Access to food and the level of corticosterone, and pre-exposure to MWM water: free access to tap water and standard laboratory apparatus and testing procedures reduces thigmotaxis chow. The Animal Study Ethics Committee of our uni - [63, 67]. The location of the platform is not the outer versity approved all the experimental procedures used in edge of the MWM tank,so MWM performance may be this study. Also, all experimental procedures were done in indirectly disrupted by thigmotaxis [67, 68]. accordance with the National Institutes of Health Guide It is important to understand that there is a link for Care and Use of Laboratory Animals. Every effort was between estradiol levels in females and better perfor- made to minimize suffering. Actions that can cause pain mance in spatial skills, so that lower estradiol levels and distress were done in the absence of other animals in females lead to better performance in rodents and in another room. Intraperitoneal injection of urethane in women [69, 70]. Since stress rises estradiol levels in (ethyl carbamate, 1.5 g/kg; i.p.) was used for anaesthetiza- females [71], this stress exposure may increase estradiol tion of rats. levels and lead to poorer performance in females than males. Another possible mechanism for better performance Morris water maze (MWM) task of male rats than females is that calcium/calmodulin- Apparatus dependent protein kinase kinase β (CaMKKβ) has an The MWM test, a hippocampal-dependent test, is used male-specific role in the processes of memory forma - to assess spatial learning and memory in rodents [75– tion [72]. Additionally, CaMKKβ has been revealed to be 78]. The main advantage of MWM task is the distinc - essential for the activation of hippocampal cyclic AMP- tion between spatial conditions (hidden platform) and responsive element binding protein (CREB) by spatial non-spatial conditions (visible platform). Furthermore, training, and to contribute to hippocampal LTP in male the MWM test environment decreases odor trail inter- mice [73]. These observations suggest that hippocampal ference. The MWM device consisted of a black circular memory consolidation mechanisms are different between pool with a diameter of 155 cm and a height of 60 cm, the sexes. which was filled with water at a temperature of 22 ± 1 °C LTP has been reported to be dependent on nitric to a depth of 35 cm. The pool was divided into four equal oxide synthase-1 (aNOS1) signaling in males (but not in quadrants. An invisible platform with a diameter of females) [74]. Lack of nitric oxide (NO) and decreased 10 cm, made of clear Plexiglas, was placed in the center hippocampal NOS1 expression in the female are the main of the eastern quarter as the target quadrant at a dis- causes of this sex difference [74]. However, NO-depend - tance of 2 cm below the water surface. A video-computer ent LTP appears to be a secondary mechanism for LTP tracking system (CCD camera, Panasonic Inc., Japan) induction in females, but is more important in males. was used to record the rats’ swim path for further analy- sis (EthoVision software XT7, Netherland). Large posters were used on the wall of the room as visual cues. Scheme Conclusion of the MWM protocol is shown in Fig. 7. In summary, our results showed that there was sex dif- ference in LTP in PP-DG synapses, which was higher in male than female rats. Therefore, our study suggests that Habituation sex associated difference in LTP may contribute to sex In order to adapt the rats to the MWM test, one day difference in spatial learning and memory. Lack of deter - before the starting of training, the rats swam for one min- mination of the estrous cycle stage and the corticosterone ute in a tank without a platform. S afari et al. Behav Brain Funct (2021) 17:9 Page 7 of 11 W E W Starts: S-N-E-W Hidden Platform Training Visible Platform Test Day 1 Day 2 Day 3 Day 4 Day 5 Day 5 44 trials/day trials/day 4 trials/day 4 trials/day 30 min after T1 T2 T1 T2 T1 T2 T3 T1 T2 T3 T4 T3 T4 T4 T3 T4 No Platform probe test Habituation Probe Test W E Fig. 7 Scheme of the MWM protocol. Scheme of the Morris water maze protocol indicating habituation, hidden platform training, probe test or retention and visual test. An empty circle shows a hidden platform position. The red circle shows a visible platform position. Dashed lines represent imaginary quadrant boundaries Hidden platform training for 60 s in a pool without platform. The animals were The training sessions were done according to our earlier released into the water in the western quadrant (ie, works [75, 77, 79–81]. Briefly, the training session was exactly opposite from where the platform was placed in conducted for four consecutive days (one block of 4 tri- the training sessions). A video-computer tracking sys- als per day). Each trial began by putting the rat in the tem was used to record the distance traveled and time middle of one of the four quadrants. The swimming time spent in target zone as well as swimming speed of rats to find the hidden platform was 90 s. If the animal did (to evaluate the motor activity). not find the hidden platform during this period, it was manually transferred to the platform by the investigator. The time between the two consecutive trials was 10 min. Visual test To assess acquisition of the MWM task during training Thirty minutes after the probe trial, visual test was per - days, escape latency (i.e., time to reach the platform) and formed. In the visual test, the platform was covered swimming distance were recorded. The daily average of with bright color aluminum foil and placed in a differ - all trials from day 1 to day 4 was used in our analysis. ent zone above the water surface. In the visual test, rats swam for 60 s to find the visible platform in order to Spatial reference memory (Probe test or retention) test their visual ability. All experiments were performed The spatial probe test was performed one day after the between 12:00 and 14:00. last training session. In the spatial probe test, rats swam Safari et al. Behav Brain Funct (2021) 17:9 Page 8 of 11 Surgical procedure, electrophysiological recording and LTP Measurement of evoked potentials induction PS and fEPSP are two components of the evoked record- The procedures used here were done according to our ing in the DG. In our work, PS amplitude and fEPSP slope previous works [82–84]. Briefly, after urethane anesthe - were measured. The PS amplitude was measured from sia (1.5 g/kg, i.p), the rats were placed in a stereotaxic the peak of the first positive deflection of the evoked device for electrode implantation surgery and field potential to the peak of the following negative potential. potential recording. Using a heating pad, the tempera- The fEPSP slope function was measured as the slope of ture of the animals was kept constant at 36.5 ± 0.5 °C . the line connecting the start of the first positive deflec - After the skull is exposed, small holes were drilled tion of the evoked potential with the peak of the second in the skull, and then two bipolar stimulating and positive deflection of the evoked potential. The stimula - recording electrodes were implanted in the right cer- tion intensity was adjusted to evoke potentials which ebral hemisphere. The electrodes were made of Teflon comprised 40% of the maximal population spike ampli- coated stainless steel (125 µm diameter, Advent Co., tude, defined by means of an input/output curve [82, 83]. UK). The coordinates for electrode placement were as follows (according to the Paxinos and Watson atlas of the rat brain [82, 85]): Stimulating electrode in the PP Statistical analysis [:AP: − 8.1 mm from bregma; ML: + 4.3 mm from mid- GraphPad Prism 8.0.2 software (San Diego, CA, USA) line; DV: 3.2 mm from the skull surface], and recording was used for statistical analysis. Data were presented as electrode in the DG granular cell layer [AP: − 3.8 mm means ± standard error mean (S.E.M.). The data of the from bregma; ML: + 2.3 mm from midline; DV: 2.7– training trials in MWM were analyzed using a two-way 3.2 mm from the skull surface]. To minimize damage analysis of variance (ANOVA) (followed by Bonferoni to the brain, the electrodes were lowered very slowly post hoc) with days as repeated measures factor and (0.2 mm/min) from cortex to the hippocampus. treatments as between subjects’ factor. Student t-test was We obtained input–output profile by PP stimula - used for statistical analyses of probe and visibility trial tion to determine the intensity of stimulus used in data. Two-way repeated-measures ANOVA followed each animal (40% maximal population spike). Through by Bonferroni post hoc was used for analysis of the LTP constant current isolation units (A365 WPI), single data. Student t test was used when only two values were 0.1 ms biphasic square wave pulses were delivered at compared. P values below 0.05 were considered statis- a frequency of 0.1 Hz. The field potential recordings tically significant. The following formula was used to evoked by stimulation of the PP were recorded extra- determine LTP values: cellularly in the DG area. Test stimuli were delivered to the EPSP or PS value after HFS induction × 100% the PP every 10 s. Electrodes were positioned to elicit LTP = the average EPSP or PS at baseline the maximum amplitude of PS and fEPSP. After record- ing the steady-state baseline response for 40 min, LTP Acknowledgements was induced using the 400 Hz HFS (including10 bursts The authors would like to express their gratitude to the staff of the Neuro ‑ of 20 stimuli, 0.2 ms stimulus duration, 10 s interburst physiology Research Center for helping them carry out this project. interval). DG granular neurons were recorded at 5, 30, Authors’ contributions and 60 min post-HFS stimulation to determine any SAK supervised the project. SAK, AK, IS, and SS and designed the project, change in the both fEPSP and PS. An average of 10 con- wrote the manuscript and performed the statistical analysis and revised the secutive recordings were made at 10 s stimulus inter- manuscript. SS, NA, RM, RG and MKA were involved in laboratory works and experimental design of the work. SAK AK, and IS were involved in data collec‑ val for each time point [83, 86, 87]. For stimulations, tion and lab assessments, and study designing. All authors read and approved stimulus parameters were defined in the software at the final manuscript. the beginning and prior delivery to PP, then sent via a Funding data acquisition board connected to a constant current The study was funded by Vice‑ chancellor for Research and Technology, Hama‑ isolator unit (A365 WPI, USA). The evoked responses dan University of Medical Sciences (No. IR.UMSHA.REC.1400.201). in the DG region after passing through a preamplifier, Availability of data and materials were amplified (1000 ×) (Differential amplifier DAM The data are available for any scientific use with kind permission. 80 WPI, USA), and were filtered (band pass 1 Hz to 3 kHz). These responses were digitized at a sampling Declarations rate of 10 kHz, and were observable on a computer monitor. These responses were stored in a high-speed Ethics approval and consent to participate The Animal Study Ethics Committee of our university approved all the experi‑ data storage device for later offline analysis. mental procedures used in this study (Code of Ethics Committee: IR.UMSHA. REC.1400.201). Also, all experimental procedures were done in accordance S afari et al. Behav Brain Funct (2021) 17:9 Page 9 of 11 with the National Institutes of Health Guide for Care and Use of Laboratory 18. Coluccia E, Louse G. 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Journal
Behavioral and Brain Functions – Springer Journals
Published: Nov 1, 2021
Keywords: Long-term potentiation; Hippocampus; Dentate Gyrus, Spatial learning and memory; Sex difference; Wistar Rat