Learned H e lp le s s n e s s is an acce p ted m odel o f d e p re ssio n ( O v e rm ie r & S e lig m an 1967). A cute stress e x p o su re results in an inhibition o f LTP in brain areas such as the C A l region o f the h ip p o c a m p u s (X u et al. 1997). T herefore, it w as h y pothesised that there m ay be diffe re nc es in the plasticity properties betw een different specially bred subgroups o f rats that w ere differentially susceptible to the learned helplessness m odel o f d e p re s s io n . It w a s h y p o th e s is e d that a n im a ls th at w e re r e s is ta n t to lea rn ed h elplessness (c N L H ) w o u ld have norm al LTP w hile those a n im a ls w h ic h ha v e an inherent tendency to learned helplessness, exhibiting a helpless p h e notype even in the a bsence o f u n c o n tro lla b le shock (cL H ) w ould show im paired LTP induction. Upon in v es tig a tio n , it w a s d is c o v e r e d that a n im a ls w h ic h w ere c o n g e n ital n o n -le a rn e d h e lp le s s and e x p re s s e d a n o n -le a rn e d h e lp le ss p h e n o ty p e elic ite d a sm all albeit significant a m ount o f potentiation post HFS. Interestingly, congenital learned helpless a n im a ls , e x p re s s in g e ith e r a learned or n o n - le a rn e d h e lp le s s p h e n o ty p e e lic ite d num erically g rea ter LTP post HFS than did the learned helpless resistant group. This increase bordered on statistical significance (cI,H-lh/nlh vs cN L H -nlh, p=0.057). This finding is s o m e w h at surprising and the reasons for it are unclear. This animal m odel is based on selective breeding and therefore it may be that the genetic difference betw een strains m ay account for this tendency for a difference in LTP induction. Diversity o f the gene pool is ensured by using repeated back crosses to the paternal strain which should red u c e the lik e lih o o d o f incidental c o -s e le c tio n o f g e n e s not rela te d to learned helplessness. Interestingly, the level o f LTP does not seem to be d e p e n d en t on the behavioural p h e n o ty p e expressed as there was no statistical difference in LTP induced betw een cLH -lh and cL H -nlh anim als (p>0.5). In addition, neither cLH nor cN LH rats show any h ip p oca m pal-depe nde nt learning deficits (V ollm ayr et al. 2004).
As expected, HFS induced LTP in outbred Sprague D aw ley control rats that were not b e h a v io u ra liy tested. In contrast, statistically sig n ific a n t LTP w as not induced in o utbred S pra gue D a w le y a nim als exposed to the ‘training and t e s t in g ’ protocol for learned h e lp le s sn e s s . T h u s the m a g n itu d e o f p o te n tia tio n in the S p ra g u e D a w le y
outbred control anim als was significantly greater than in those anim als that underw ent the ‘training and te s t in g ’ procedure. I'h is possibly suggests an e xpla na tion for the unexpected results o f the congenital learned helplessness study. The training session involves exposure to 20 m inutes o f unpredictable and uncontrollable shock within a 40 m inute period. T he testing procedure involves the delivery o f 15 controllable shocks each o f a m a x im u m duration o f 60 seconds term inable using a lever by the anim al. Previously, Shors et al. (1989) reported that LTP in h ippoca m pal slices o f anim als exposed to inescapable shock was impaired com pared to that o f anim als exposed to the sam e a m ount o f controllable shock. This suggests that the context o f stress exposure (controllable vs uncontrollable) in relation to its effect on subsequent LTP induction m ay be o f greater im portance than the absolute a m o u n t o f shock delivered. cN LH a n im a ls re c e iv e d both the tra in in g a n d tes tin g . T h e r e f o r e th ey re c e iv e d both controllable and uncontrollable shock. cLH anim als o f either behavioural phenotype (Ih or nlh) received testing only, i.e. they received only controllable shock. H ow ever there was no significant correlation betw een LTP induced and am o u n t o f escapable shock exposure. Taken together, this suggests that the unexpected result o f a tendency for r e d u c e d level o f L T P in c N L H a n im a ls is p o s s ib ly a re s u lt o f e x p o s u r e to unc o n tro lla b le shock (as part o f the tra in in g p ro c e d u re ) and m ay not n e c essa rily indicate a real difference betw een the cL H and cN L H anim als with respect to LTP induction. The results in the outbred Sprague Daw ley rats suggest that the exposure to uncontrollable shock results in prolonged inhibition o f the induction o f LTP at synapses in the C A l area. Indeed, there w as a significant reduction in LTP betw een all anim als that received ‘tra ining and t e s t in g ’ both o u tb re d and congenital anim a ls and those outbred and congenital anim als that r e c e iv e d testing only (p<0.05). O u r finding is c onsistent with V o llm a y r et al. (2004) w h o rep o rted that cLH and cN L H anim als h a v in g u n d e rw e n t the sa m e ‘tra in in g and t e s t i n g ’ p r o c e d u r e as o u tlin e d in o u r experim ents show ed no difference in their perform a nc e in the M orris W ater M aze (a hippo ca m p al-d ep e n d e n t learning paradigm ). It m ay be that the tendency for reduced LTP in the C A l area o f cN L H anim als is sim ply a result o f plasticity b e ing m ore sensitive to the differences betw een controllable and uncontrollable shock than is the Morris W ater M aze task. H ow ever, King et al. (2001) reported that in naive cLH and
cNLH animals (i.e. no training or testing), cNLH animals showed a significantly reduced latency to find the platform in the Morris Water Maze when compared to cLH animals. Furtherm ore following exposure o f both groups to the same am ount o f uncontrollable stress cNLH animals showed enhanced performance in this task as opposed to the further compromised performance o f the cLH animals. Therefore, it would be interesting in future studies to investigate naive cLH and cNLH animals (i.e. no training or testing) with respect to LTP induction in C A l.
Alternatively, differences in various transmitter systems between learned helpless and non-learned helpless animals may contribute to the tendency for reduced LTP induction in cNLH animals and should be investigated. Hippocampal slices from Sprague Dawley rats in which learned helplessness was induced by uncontrollable shock exposure show a significant increase in both endogenous and K -stimulated serotonin release (Edwards et al. 1992). Also such learned helpless animals have upregulation o f beta-adrenoceptors in the hippocampus (Martin et al. 1990). Moreover learned helpless rats show up regulated 5-H Tjb receptors in the hippocampus, cortex and septum (Edw'ards et al. 1991). Similar alterations in monoaminergic receptors are observed in cLH animals (Henn et al. 1993). cLH animals also have upregulated u opioid receptors in the hippocampus and cortex. These receptors are down regulated in the hypothalamus (Henn et al. 1993). cLH animals also have altered intracellular signalling when compared to Spague Dawley or cNLH animals. Vollmayr et al. (2001) reported that there was no difference in BDNF mRNA levels in either the dentate or CA3 region o f the hippocampus. They further reported that following exposure to restraint stress only the cLH group failed to show a decrease in BDNF levels. BDNF itself is important for the expression o f LTP in the hippocampus (Patterson et al. 1996) and alterations in its expression may account for the tendency for larger LTP in the cLH groups than in cNLH groups.
There was no significant difference in the current required to elicit a 50% maximum EPSP between groups. Furthermore there was no statistically significant difference
betw een any group w ith respect to test EPSP am plitude. T herefore, it appears that there w ere no basal differences betw een groups in respect o f baseline synaptic transm ission.
All gro u p s elic ite d PPF at all interstim u lu s in tervals tested . T h e re w as no sig n ific a n t difference betw een groups. As PPF is sensitive to differen ces in g lu tam ate release this suggests th at th ere is no d ifference in the presy n ap tic p ro p erties o f the synapses in the C A 1 area betw een these groups.