TY - JOUR
AU - Manahan-Vaughan, Denise
AB - Abstract Hippocampal long-term depression (LTD) comprises a persistent decrease in synaptic transmission which is induced by repeated low-frequency stimulation (LFS). Although LTD has been widely demonstrated in the CA1 region in vitro, very few positive reports of LTD in vivo have occurred. In this study, the conditions under which homosynaptic LTD occurs in the CA1 region of freely moving rats was investigated. Three rat strains were studied: Wistar, Sprague– Dawley and Hooded Lister. Whereas Wistar and Sprague–Dawley rats expressed optimal LTD following 1 Hz LFS, Hooded Lister rats showed no LTD when tested in an LFS range of 1–10 Hz. Exposure to marked stress transiently enhanced LTD obtained in Wistar and Sprague–Dawley rats, but did not facilitate LTD induction in the LTD-resistant strain. It was possible to induce long-term potentiation with high-frequency stimulation, although the profile of LTP was different in each strain. These data suggest that the expression of LTD varies according to the strain of rat used and is tightly dependent upon stimulation frequency. In addition the behavioral state of the animal may influence LTD expression. These data may explain, in part, the conflicting reports with regard to the inducibility of hippocampal LTD in vivo. Introduction The concept that long-term potentiation (LTP) could have a counterpart in long-term depression (LTD) and that both forms of synaptic plasticity cooperate together to enable information storage in the hippocampus has existed for a number of years (Christie et al., 1994; Bear, 1996). LTD could thus, for example, either serve as a means to unsaturate LTP — thereby perhaps preventing memory saturation — or play a role in forgetting (Tsumoto, 1993). Alternatively LTD could underlie distinct forms of information storage. An important criterion for the role of LTD in such memory-related processes is that LTD occurs in vivo in the freely moving rat. However, recent reports with regard to LTD induction in the CA1 region of the hippocampus in vivo are controversial. Whereas the induction of LTD in hippocampal slices in vitro has been widely reported (Mulkey and Malenka, 1992; Dudek and Bear, 1992; Bashir et al., 1993; Christie et al., 1994), hippocampal LTD induction in vivo has proven to be less consistent. Whereas some have indicated failure to induce LTD in vivo (Errington et al., 1995; Doyle et al., 1997), others have shown successful induction in anesthetized or freely moving rats (Heynen et al., 1996; Thiels et al., 1996; Manahan-Vaughan, 1997), or in awake rats which have been previously stressed (Xu et al., 1997). As a result, a possible role for this form of longterm synaptic modification in information storage processes in the hippocampus has been cast into doubt. One possibility is that the variations in rat strain used could influence LTD induction. To investigate this, in the present study a comparison was made between CA1 LTD induction in three rat strains: Wistar, Sprague–Dawley and Hooded Lister. Recently, robust LTD following prolonged 1 Hz stimulation was reported in the CA1 region of freely moving Wistar rats (Manahan-Vaughan, 1997). We thus compared the effect of various low-frequency stimulation (LFS) protocols on LTD induction in this strain, with LTD induction in Sprague–Dawley and Hooded Lister rats. Furthermore, the expression of LTP in these rat strains was evaluated. Stress may play a role in LTD induction (Xu et al., 1997). Therefore, we investigated whether LTD expression following LFS was altered following exposure of the three strains to a protocol which should induce marked stress (Balfour and Reid, 1979; Xu et al., 1997). The aim of this study was thus to attempt to characterize LTD in three rat strains, in an effort to help clarify the inconsistency of reports from different laboratories as to the inducibility of LTD in vivo. Materials and Methods Electrode Implantation Male Wistar, Hooded Lister or Sprague–Dawley rats (7–8 weeks old at the time of surgery) were chronically implanted with electrodes under pentobarbitone anesthesia (40 mg/kg, i.p.) as described previously (Manahan-Vaughan, 1997). Briefly, under physiological control, a recording electrode was lowered into the CA1 region and a pair of stimulating electrodes were placed in the Schaffer collaterals of the right dorsal hippocampus through holes drilled through the skull. A ground and a reference screw were inserted in the bone of the skull. The entire assembly was connected to a rubber socket on the animal's head and then stabilized using dental cement. Preliminary electrophysiological and histological investigations were carried out to establish the electrode localization sites in the three strains. Findings indicated that slightly different electrode coordinates to those used for the Wistar and Hooded Lister strains were needed to enable recording and stimulation at equivalent locations in the CA1 region of Sprague–Dawley rats. The coordinates for the Wistar and Hooded Lister strain were: recording electrode, 2.8 mm posterior to bregma, 1.8 mm lateral to the midline; stimulating electrodes, 3.1 posterior to bregma, 3.1 lateral to the midline. The coordinates for the Sprague–Dawley strain were: recording electrode, 3.4 mm posterior to bregma, 2.0 mm lateral to the midline; stimulating electrodes, 3.5 posterior to bregma, 3.0 lateral to the midline. The correct placement of the electrodes into the CA1 region of each individual rat was confirmed after the end of each study post-mortem histological analysis. Electrophysiology After surgery the animals were allowed 7–10 days to recover, then acclimitization to the recording chamber (40 × 40 × 40 cm) for 24 h was permitted. A cable which was attached via a swivel connector to an amplifier was inserted into the socket on the animal's head. The animal could move freely during recordings. Field excitatory post-synaptic potentials (fEPSPs) were evoked using square wave stimulation (0.2 ms) at 0.025 Hz. For each time-point the average of five evoked responses was used. At the beginning of each experiment input/output curves were plotted to determine the maximum evoked fEPSP slope. For measurement of basal synaptic transmission, a stimulus intensity was used which evoked a response which was 40% of this maximum fEPSP slope. Experiments where basal synaptic transmission was monitored were carried out at least 24 h before LTD or LTP experiments were conducted. LTD was evoked using 900 pulses at 1, 2, 3, 5 or 10 Hz. LTP was evoked using 100 Hz stimulation (10 bursts at 10 s intervals). In this study, LTD was defined as a significant reduction of synaptic transmission which endured for >4 h. Conversely, LTP was defined as a significant increase of synaptic transmission which endured for >4 h. Data were expressed as mean ± SEM baseline fEPSP, and statistical analysis was conducted using Student's t-test. Cortical electroencephalogram activity (EEG) was constantly monitored throughout the experiments. Whereas no alterations in EEG were associated with test pulse, 1, 2, 3, 5 or 100 Hz stimulation, application of 10 Hz stimulation was associated with epileptiform activity. Stress Induction Twenty-four hours after recording, naive animals were placed in the recording chamber and input/output measurements were taken, followed by a 30 min baseline recording. Animals were then placed on a transparent platform (20 cm diam) at the top of a pillar, 105 cm above the ground, in the middle of a brightly lit room for 30 min. LFS (1 or 3 Hz, 900 pulses) was then given within 5 min of removal from the platform. Results LTD in the CA1 Region In Vivo is Frequency- and Strain-dependent In all three rat strains basal synaptic transmission was stable over the 24 h period observed (Fig. 1a; Wistar, n = 8; Hooded Lister, n = 8; Sprague–Dawley, n = 6). In Wistar rats, an inverse relationship between stimulation frequency and LTD induction in the CA1 region was found. Maximal LTD, which endured for >24 h, was seen with 1 Hz stimulation (900 pulses, Fig. 1b, n = 10), with less LTD occurring in the range of 2–10 Hz (Fig. 1c, Table 1). Thus the depression induced by 2 Hz stimulation endured for <24 h (Fig. 1c, n = 5) whereas short-term depression (STD) of <2 h was induced by stimulation at 3 or 5 Hz (Table 1). In each of the three strains, 10 Hz stimulation (900 pulses) produced head-shaking and signs of EEG disruption (epileptiform activity). In some cases evoked potentials were abolished. Lowering the number of pulses given during 1 Hz stimulation reduced the persistence of LTD obtained (Table 2), whereas increasing the number of pulses did not improve either the magnitude or the duration of LTD obtained when compared with 900 pulses. In Sprague–Dawley rats optimal LTD was elicited with 1 Hz given 900 times (n = 7). However, the magnitude of LTD obtained was smaller than that seen in Wistar rats (Fig. 1b). Furthermore, LTD induced by 1 Hz stimulation persisted for 5–7 days in Sprague–Dawley rats (data not shown), whereas 1 Hz induced LTD which endured for at least 7 days in Wistar rats (Manahan-Vaughan and Braunewell, 1999). The relationship between stimulation frequency and expression of LTD appeared to be more sensitive in the Sprague–Dawley strain, with only a 3 h STD occurring with 2 Hz stimulation (Fig. 1c, n = 4), and no depression at all occurring with 3–10 Hz stimulation (Table 1). The STD obtained with 2 Hz stimulation was significantly different from t = 5 min until t = 4h post-LFS (P < 0.05) from that obtained in Wistar rats. Hooded Lister rats showed only STD when exposed to 1 (n = 8) or 2 Hz (n = 6) stimulation (Fig. 1b,c). The recovery of fEPSP values to basal levels was more rapid following 2 Hz stimulation. The slight reduction in evoked values seen 24 h after 2 Hz stimulation was not significantly different from basally stimulated controls. The magnitude of initial STD elicited by 1 and 2 Hz stimulation was not different from that seen in the Wistar rats. No response at all to higher frequencies of stimulation was seen in the Hooded Lister rats; rather, responses were not significantly different from basal synaptic transmission in these animals (Table 1). LTP is Expressed in All Three Rat Strains, although Different Profiles are Evident It was previously demonstrated that robust LTP can be induced in Wistar rats by high-frequency stimulation (Manahan-Vaughan, 1997). This protocol was applied (100 Hz, 10 bursts of 10 stimuli, 0.1 ms stimulus duration, 10 s interburst interval) to compare LTP expression in the three rat strains. It was found that LTP could be induced with 100 Hz stimulation in all three strains (Fig. 2). However, the profile of LTP expressed was different in each strain. Wistar rats expressed short-term potentiation (STP) with the greatest magnitude. Initial STP in the Wistar strain was 157 ± 5% of pre-tetanus values, compared with 123 ± 3% in Sprague–Dawley rats and 124 ± 3% in Hooded Listers. Whereas the STP in Hooded Lister rats gradually increased to reach equivalent LTP levels in the Wistar rats (P < 0.01 from t = 5 min until t = 60 min post-tetanus compared with Wistar LTP values), LTP in Sprague–Dawley rats remained significantly smaller than that seen in Wistar rats during the recording period (P < 0.01 compared with Wistar LTP values throughout the recording period). Twenty four hours after tetanization fEPSP slope values were 146 ± 6% of pre-tetanus values in Wistar rats (P < 0.01 compared with controls), 135 ± 7% of pre-HFS values in Lister rats (P < 0.05 compared with controls) and 117 ± 1% of pre-HFS values in Sprague–Dawley rats (P < 0.05 compared with controls). Thus, although LTP occurred in each of the three rat strains, certain differences in the profile of LTP were evident. Exposure of the Rat Strains to Stress Enhances STD in LTD-expressing Strains, but Does not Enable LTD Induction in the Resistant Strain It has been reported that stress exposure inhibits LTP and facilitates LTD expression in vivo (Diamond et al., 1994; Xu et al., 1997). Thus, increasing stress in the LTD-resistant (Hooded Lister) strain could perhaps enable the expression of LTD following LFS or enhance LTD expression in Wistar and Sprague–Dawley rats. This would not only provide evidence that strain-dependent differences in stress perception could account for differences in LTD expression, but would also suggest that stress and LTD expression are tightly linked. To determine whether exposure of the rat strains to stress could influence subsequent induction of LTD, animals were exposed to a protocol of stress induction which had been shown to facilitate LTD in vivo (Xu et al., 1997). Thus, following measurement of input/output curves and an initial baseline recording, animals were placed in an elevated platform for 30 min. This protocol should induce marked stress in rats (Balfour and Reid, 1979; Xu et al., 1997). In the present study, exposure to the elevated platform produced behavioral evidence of stress, in the form of urination, defecation and ‘freezing’ behavior. No apparent difference in the behavior of the three strains during platform exposure was noted. However, a differential stress hormone response in the three rat strains may have been induced by platform exposure (Manahan-Vaughan and Braunewell, 1999). Five minutes after removal from the platform, LFS at 1 Hz was given. Figure 3a represents the fEPSP values of rats which have undergone this stress protocol (whereas in Fig. 1b, the fEPSP values of non-stressed rats are depicted). In Wistar rats an initial difference in the degree of STD obtained was seen. Five minutes after LFS the fEPSP value was 43 ± 6% (n = 6), compared with 59 ± 4% in non-stressed controls (n = 10, P < 0.05, Fig. 3a). Values remained statistically significant until 45 min post-LFS, when fEPSP slope values in the stressed group reached levels similar to the non-stressed group. Twenty four hours after LFS the fEPSP value was 69 ± 9%, compared with 73 ± 5% in non-stressed controls. Application of test pulses (0.025 Hz) to evoke basal synaptic transmission instead of 1 Hz stimulation after exposure to the platform induced no significant changes in synaptic transmission in Wistar (n = 4), Hooded Lister (n = 4) or Sprague–Dawley rats (n =4, data not shown). In Sprague–Dawley rats a slight enhancement of both STD and LTD was seen when 1 Hz LFS was given following the stress protocol (Fig. 3a). Five minutes after LFS the fEPSP value was 61 ± 1%, compared with 72 ± 3% in non-stressed controls (P < 0.05). The significant difference in stressed versus non-stressed fEPSP slope values persisted until 4 h post-LFS. Twenty-four hours after LFS the fEPSP value was 74 ± 4% (n = 4), compared with 88 ± 5%, in non-stressed controls (n = 7, not significant). In Hooded Lister rats a prolongation of the depression expressed was seen when 1 Hz LFS was given following the stress protocol (n = 5). Thus, although no initial difference in STD was seen in the stressed and non-stressed groups, a statistical difference became obvious at t = 60 min post-LFS (66 ± 7%, compared with 84 ± 5% in non-stressed controls, n = 8, P < 0.05) which was still present t = 180 min post-LFS (80 ± 9%, compared with 104 ± 4% in non -stressed controls, P < 0.05). By t = 195 min post-LFS fEPSP slope values for the stressed and non-stressed groups were no longer significantly different from each other. LFS-induced depression in stressed animals was also significant from t = 5min until t = 180 min post-LFS, compared with basally stimulated controls (n =8, P < 0.01). Thus, although LTD was not expressed, stress exposure prolonged STD in Hooded Lister rats. The facilitatory effects of stress on LTD were also investigated using a 3 Hz (900 pulse) stimulation protocol. Thus, LFS at this frequency was tested, in Wistar and Hooded Lister rats, following the stress protocol. In Wistar rats no improvement in the depression induced by 3Hz LFS was seen compared with control animals (n = 4, Fig. 3b). Whereas no STD was seen following 3 Hz LFS in non-stressed Hooded Lister rats, a significant STD was observed when LFS was given following the stress protocol (n = 4). fEPSP values were significantly different from controls, which received 3 Hz only from t = 5 min until t = 165 min post-LFS (P < 0.01, Fig. 3b). Thus exposure of the Hooded Lister rats to stress was insufficient to facilitate LTD, although stress did appear to lower the threshold for induction of STD. In addition, stress slightly enhanced the depression expressed in Wistar and Sprague– Dawley rats (following 1 Hz LFS), although no long-term effects on LTD expression were seen. Discussion The results of this study clearly show that LTD in the CA1 region in vivo is strain-dependent. Thus, Wistar and Sprague–Dawley rats express LTD following LFS, but Hooded Lister rats are LTD-resistant. The data also indicate that the expression of LTD is modulated by the behavioral state of the animal. The experience of stress appears to lower the threshold for LTD, enabling a transient enhancement of STD and/or LTD expression in the strains which normally express LTD, and causing the facilitation of STD expression in the LTD-resistant strain. However, stress alone does not facilitate LTD expression in LTD-resistant rats. The behavioral state may, however, play a critical role in the expression of LTD in vivo. In this study optimal LTD was induced in Wistar and Sprague– Dawley rats when 1 Hz LFS was given 900 times; application of other frequency protocols induced either a less robust form of LTD, STD or no response. In addition, it was found that the Hooded Lister rat strain did not exhibit LTD in response to these stimulation protocols, and at best expressed STD when stimulated at 1 or 2 Hz. Thus, LTD was not only frequency-dependent but also appears to vary according to the strain of rat involved. Although LTD was clearly induced in Wistar and Sprague– Dawley rats by a 1 Hz LFS protocol in this study, it should be pointed out that difficulties in induction of LTD have been reported in both Wistar and Sprague–Dawley rats (Errington et al., 1995; Doyle et al., 1997; Xu et al., 1997). Furthermore, inbreeding and cross-breeding within strains has in itself produced marked variations between strains of the same apparent name (Becker et al., 1993; Kacew and Festling, 1996). This complicates comparisons between attempts to induce LTD in rats of the same strain (originating from different sources) in different laboratories, but emphasizes how critical genetic background can be in determining the inducibility of this form of synaptic plasticity with LFS. It is unlikely that differences in motor activity could account for the strain-dependence of LTD induction seen in the rat strains. Studies which previously investigated the relationship of motor activity to hippocampal fEPSP magnitude found that fEPSPs evoked during movement were significantly smaller in magnitude than those evoked during immobility (Winson and Abzug, 1978; Brankack and Buzsaki, 1986; Hargreaves et al., 1990). Although differences in the motor activity of the three rat strains were noted upon initial introduction to the recording chamber 24 h before experiments were begun, Hooded Lister rats showed the most activity and Wistar rats the least. During the recording session, all three strains were quietly alert: tending to rest in a corner of the recording chamber and show little behavioral activity. However, 1 Hz stimulation was associated with increased arousal in all three strains. Once more Hooded Lister rats were the most active and Wistar rats the least [data not shown, but see (Manahan-Vaughan and Braunewell, 1999)]. Thus it is improbable that the differences in LTD seen among the strains could be accounted for by activity-modulation of EPSP magnitude, as the strain which demonstrates the weakest LFS-induced synaptic depression is the strain which demonstrates the most motor activity. Although it has been reported that exposure to stress can facilitate the induction of LTD in an LTD-resistant rat strain (Xu et al., 1997), the present study demonstrated that whereas stress can perhaps modulate the threshold for LTD induction, it is not the key factor in determining whether LTD is expressed. In the LTD-resistant rats, exposure to stress lowered the threshold for STD induction but did not enable LTD expression. In LTD-expressing rats, the early phases of LTD were slightly enhanced by exposure to stress, although no long-term effects on LTD expression were seen. The influence of stress on LTD expression has been correlated to elevations in serum corticosterone levels caused by the stressful experience (Xu et al., 1997). Furthermore, in another study, it was found that serum corticosterone levels were significantly increased compared with basal levels in Wistar and Hooded Lister rats following exposure to the platform protocol for 30 min (Manahan-Vaughan and Braunewell, 1999). Corticosterone has diverse effects in the hippocampus, but effects such as enhancement of currents through voltagegated calcium channels (Coussens et al., 1997) and modulation of N-methyl-d-aspartate channels (Sapolsky, 1986; Talmi et al., 1995) are possible mechanisms by which corticosterone could lower the threshold for LTD expression. However, ‘stress' in the classical sense is not the only means by which corticosterone levels can become elevated. Indeed, it should be pointed out that serum corticosterone levels can become elevated, to levels equivalent to those induced by stress, through events such as exposure to sudden changes in ambient temperature (Yi and Baram, 1994; Bramham et al., 1998), fluctuations in the circadian cycle (McEwen et al., 1986; Joels and de Kloet, 1994), the receipt of food when hungry (Krieger, 1974; Honma et al., 1984) or a receptive sexual partner (Taylor et al., 1987). Thus the modulation of LTD by corticosterone does not necessarily have to be a consequence of psychological stress or distress, but, rather, may be determined by the relative behavioral state of the animal. The finding that stress alone is not sufficient to enable LTD expression in LTD-resistant rats suggests, however, that factors other than corticosterone elevation are involved in the induction of LTD in vivo. To confirm that other forms of synaptic plasticity were possible in the three rat strains studied, high-frequency tetanization was given to induce LTP. LTP was expressed in all three rat strains. Interestingly, however, the profile of LTP was different for each strain. Whereas Wistar rats expressed the largest and most robust LTP, Sprague–Dawley expressed LTP which was significantly smaller in magnitude than that seen in Wistar rats. Furthermore, Hooded Lister rats expressed STP which was significantly smaller than the STP seen in Wistar rats, but which gradually increased in magnitude to ultimately match the LTP evoked in the Wistar rats. Both LTP and LTD are NMDA receptor dependent in the CA1 region (Harris et al., 1984; Dudek and Bear, 1992; Manahan-Vaughan, 1997). One could speculate, therefore, that alterations in the relative expression or responsiveness of NMDA receptors could explain the differences in both LTP and LTD expression among the rat strains studied. However, other receptor systems which are involved in the expression of hippocampal synaptic plasticity, such as the GABAergic system (Wagner and Alger, 1995; Akhondzadeh and Stone, 1996) or the metabotropic glutamate receptor system (Manahan-Vaughan, 1997, 1998), could also be involved. Strain variations among rats have been described for phenomena as diverse as cognitive performance (Diana et al., 1994; Andrews, 1996; Van der Staay and Blokland, 1996; Prior et al., 1997), hippocampal self-stimulation (Robertson et al., 1986), extent of excitotoxic damage (Lipartiti et al., 1993; Lipska and Weinberger, 1995), stress adaptation (Dhabhar et al., 1997), ventilation and metabolism (Strohl et al., 1997), brain synaptosomal Ca2+ uptake (Honda et al., 1990), neuronal density (Harris and Nestler, 1996) and brain anatomy (Schwegler et al., 1996a,b). Thus, the finding that LTD expression is strain-dependent may correlate with the strain-dependent differences in brain anatomy or functional responses seen by other researchers. Clearly the behavioral state of the animal is also an important element — as illustrated by the fact that stress enhances the depression in all three strains. However, additional factors, such as the level of arousal, attention and fatigue, may be important. Indeed, exposure to a novel environment during LFS is sufficient to induce robust LTD in the LTD-resistant Hooded Lister strain. In conclusion, the results of this study clearly demonstrate that strain variations in the expression of synaptic plasticity exist. Whereas LTP could be induced in the three rat strains studied, clear differences could be seen in the profiles of the LTP expressed by the strains. Furthermore, a striking difference in the expression of LTD was seen. Whereas Wistar rats expressed the most robust LTD, Sprague–Dawley rats expressed a persistent but less pronounced LTD and Hooded Lister rats showed only transient STD expression. In each strain, a frequency dependence in LTD expression occurred which varied according to the strain involved. Lastly, although stress exposure slightly enhanced the early phases of LTD expression in Wistar and Sprague–Dawley rats, it did not result in long-term changes in LTD expression in these strains, nor did it result in LTD induction in Hooded Lister rats. However, a significant improvement in STD was seen in this strain. Thus, although stress is probably not the key determinant of LTD expression, it clearly can modulate the threshold for LTD induction. Behavioral state may therefore comprise a crucial factor in the induction of LTD in freely moving rats in vivo. Notes This work was supported by a Deutsche Forschungsgemeinschaft grant (SFB 515/ B8). Address correspondence to Denise Manahan-Vaughan, Institute for Physiology of the Charite, Department of Neurophysiology, Synaptic Plasticity Research Group, Humboldt University, Tucholskystrasse 2, D-10117 Berlin, Germany. Email: denise.manahan-vaughan@charite.de. Table 1 Summary of the effectiveness of different stimulation protocols in inducing LTD in the hippocampal CA1 region of Wistar, Hooded Lister or Sprague–Dawley rats LFS  Wistar  Hooded Lister  Sprague–Dawley    5 min  2 h  4 h  5 min  2 h  4 h  5 min  2 h  4 h  Data represent fEPSP slope function (%) 5 min, 2 h or 4 h after LFS (900 pulses) was given. *P < 0.05, **P < 0.01, ***P < 0.001 compared with basally stimulated controls.  3 Hz  72 ± 16*  113 ± 7  100 ± 3  98 ± 7  108 ± 5  110 ± 6  89 ± 6  102 ± 3  98 ± 8        (n = 4)      (n = 6)      (n = 4)  5 Hz  77 ± 14*  111 ± 16  121 ± 12  102 ± 5  106 ± 5  109 ± 7  92 ± 9  99 ± 7  105 ± 8        (n = 4)      (n = 4)      (n = 4)  10 Hz  94 ± 15  103 ± 3  98 ± 2  96 ± 9  101 ± 6  97 ± 5  90 ± 19  97 ± 12  95 ± 6        (n = 4)      (n = 4)      (n = 4)  LFS  Wistar  Hooded Lister  Sprague–Dawley    5 min  2 h  4 h  5 min  2 h  4 h  5 min  2 h  4 h  Data represent fEPSP slope function (%) 5 min, 2 h or 4 h after LFS (900 pulses) was given. *P < 0.05, **P < 0.01, ***P < 0.001 compared with basally stimulated controls.  3 Hz  72 ± 16*  113 ± 7  100 ± 3  98 ± 7  108 ± 5  110 ± 6  89 ± 6  102 ± 3  98 ± 8        (n = 4)      (n = 6)      (n = 4)  5 Hz  77 ± 14*  111 ± 16  121 ± 12  102 ± 5  106 ± 5  109 ± 7  92 ± 9  99 ± 7  105 ± 8        (n = 4)      (n = 4)      (n = 4)  10 Hz  94 ± 15  103 ± 3  98 ± 2  96 ± 9  101 ± 6  97 ± 5  90 ± 19  97 ± 12  95 ± 6        (n = 4)      (n = 4)      (n = 4)  View Large Table 2 Summary of the effect of LFS pulse number on hippocampal LTD induction in Wistar rats (mean % ± SEM pre-LFS fEPSP) No. of pulses  5 min  2 h  4 h  *P < 0.05, **P < 0.01, ***P < 0.001 compared with basally stimulated controls.  1 Hz/100  97 ± 8  98 ± 5  102 ± 4        (n = 4)  1 Hz/300  71 ± 2***  93 ± 3  99 ± 1        (n = 4)  1 Hz/600  72 ± 9***  85 ± 5*  83 ± 2        (n = 4)  1 Hz/1200  68 ± 7***  71 ± 6*  69 ± 5        (n = 4)  2 Hz/300  100 ± 13  99 ± 9  105 ± 7        (n = 4)  2 Hz/1200  105 ± 9  103 ± 4  101 ± 6        (n = 4)  No. of pulses  5 min  2 h  4 h  *P < 0.05, **P < 0.01, ***P < 0.001 compared with basally stimulated controls.  1 Hz/100  97 ± 8  98 ± 5  102 ± 4        (n = 4)  1 Hz/300  71 ± 2***  93 ± 3  99 ± 1        (n = 4)  1 Hz/600  72 ± 9***  85 ± 5*  83 ± 2        (n = 4)  1 Hz/1200  68 ± 7***  71 ± 6*  69 ± 5        (n = 4)  2 Hz/300  100 ± 13  99 ± 9  105 ± 7        (n = 4)  2 Hz/1200  105 ± 9  103 ± 4  101 ± 6        (n = 4)  View Large Figure 1. View largeDownload slide  Differential response in synaptic transmission of three rat strains to low-frequency electrophysiological stimulation. (a) Stable basal synaptic transmission was evoked from Wistar (n = 10), Sprague–Dawley (n = 6) and Hooded Lister rats (n = 8) using test pulses. (b) LFS at 1 Hz (900 pulses) induces LTD in Wistar (n = 10) and Sprague–Dawley (n = 7) rats, but not in Hooded Lister (n = 8) rats. (c) LFS at 2 Hz (900 pulses) induces STD in Wistar (n = 5), Hooded Lister (n = 6) and Sprague– Dawley (n = 4) rat strains. Insets: field potentials (average of five consecutive sweeps) from typical experiments at the times indicated by the numbers. Horizontal bar: 5 ms; vertical bar: 2 mV. Figure 1. View largeDownload slide  Differential response in synaptic transmission of three rat strains to low-frequency electrophysiological stimulation. (a) Stable basal synaptic transmission was evoked from Wistar (n = 10), Sprague–Dawley (n = 6) and Hooded Lister rats (n = 8) using test pulses. (b) LFS at 1 Hz (900 pulses) induces LTD in Wistar (n = 10) and Sprague–Dawley (n = 7) rats, but not in Hooded Lister (n = 8) rats. (c) LFS at 2 Hz (900 pulses) induces STD in Wistar (n = 5), Hooded Lister (n = 6) and Sprague– Dawley (n = 4) rat strains. Insets: field potentials (average of five consecutive sweeps) from typical experiments at the times indicated by the numbers. Horizontal bar: 5 ms; vertical bar: 2 mV. Figure 2. View largeDownload slide  LTP of differing profiles occurs in the three rat strains. High-frequency stimulation at 100 Hz induces long-term potentiation in Wistar (n = 5), Hooded Lister (n = 8) and Sprague–Dawley (n = 4) rat strains. LTP in Hooded Lister rats was significantly different from Wistar LTP from t = 5 until t = 60 min post-tetanus (P < 0.01). LTP in Sprague–Dawley rats was significantly different from Wistar LTP from t = 5 min until the end of the recording period at 24 h min post-tetanus (P < 0.01). Line breaks indicate a change in timescale. Figure 2. View largeDownload slide  LTP of differing profiles occurs in the three rat strains. High-frequency stimulation at 100 Hz induces long-term potentiation in Wistar (n = 5), Hooded Lister (n = 8) and Sprague–Dawley (n = 4) rat strains. LTP in Hooded Lister rats was significantly different from Wistar LTP from t = 5 until t = 60 min post-tetanus (P < 0.01). LTP in Sprague–Dawley rats was significantly different from Wistar LTP from t = 5 min until the end of the recording period at 24 h min post-tetanus (P < 0.01). Line breaks indicate a change in timescale. Figure 3. View largeDownload slide  Effect of exposure to a stressful environment improves on LTD induction in Wistar, Hooded Lister and Sprague–Dawley rats. (a) Placement of Hooded Lister rats on an elevated platform for 30 min, followed 5 min later by LFS (1 Hz, 900 pulses, n = 5), enhances STD, but does not facilitate LTD induction in vivo. STD is prolonged until 180 min post-LFS in Hooded Lister rats (P < 0.05 compared with non-stressed controls, n = 8). STD is slightly enhanced in Wistar rats (P < 0.05 from t = 5 until t = 30 min post-LFS compared with non-stressed controls, n = 10), whereas LTD is transiently enhanced in Sprague–Dawley rats following exposure to the platform (P < 0.05 from t = 5 min until t = 4 h post-LFS compared with non-stressed controls, n = 7). (b) 3 Hz LFS (n = 4, 900 pulses) induced STD in Hooded Lister rats following exposure to the platform. fEPSP values were significantly different from controls which received 3 Hz only from t = 5 min until t = 165 min post-LFS (P < 0.01, n = 6). No improvement in responses to LFS is seen in Wistar rats which were exposed to 3 Hz LFS (900 pulses, n = 4) compared with 3 Hz controls (n = 4). Figure 3. View largeDownload slide  Effect of exposure to a stressful environment improves on LTD induction in Wistar, Hooded Lister and Sprague–Dawley rats. (a) Placement of Hooded Lister rats on an elevated platform for 30 min, followed 5 min later by LFS (1 Hz, 900 pulses, n = 5), enhances STD, but does not facilitate LTD induction in vivo. STD is prolonged until 180 min post-LFS in Hooded Lister rats (P < 0.05 compared with non-stressed controls, n = 8). STD is slightly enhanced in Wistar rats (P < 0.05 from t = 5 until t = 30 min post-LFS compared with non-stressed controls, n = 10), whereas LTD is transiently enhanced in Sprague–Dawley rats following exposure to the platform (P < 0.05 from t = 5 min until t = 4 h post-LFS compared with non-stressed controls, n = 7). 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TI - Long-term Depression in Freely Moving Rats is Dependent upon Strain Variation, Induction Protocol and Behavioral State
JF - Cerebral Cortex
DO - 10.1093/cercor/10.5.482
DA - 2000-05-01
UR - https://www.deepdyve.com/lp/oxford-university-press/long-term-depression-in-freely-moving-rats-is-dependent-upon-strain-duZpPErsUG
SP - 482
EP - 487
VL - 10
IS - 5
DP - DeepDyve
ER -