Neurospecific S-100 protein content in brains of different mouse strains

Total whole brain concentrations of S-100 protein and of its water-soluble fraction were determined in 11 inbred mouse straine: DBA/2J, AKR/J, CBA/Lac, C57BL/6J, C57BL/6J-Ay, C3H/He, C3H/f, DD, A/He, BALB/cLac, CC57BR/Mv, and in cerebral cortex, cerebellum and hippocampus in DBA/2J, AKR/J and CBA/Lac strains. Highly significant differences in the concentrations of the water-soluble S-100 protein were found between some strains. Slight differences were found in total S-100 protein content in whole brains between the strains (0.01 less that P less than 0.05). The DBA/2J mice had the highest brain S-100 protein content, and were characterized by a higher learning rate in shuttle-box as compared to CBA/Lac and AKR/J mice, who had a low content of this neurospecific protein.     

Comparative study of aging in the mouse olfactory bulb

Gene knockout technologies have been used to elevate the mouse as a model species. However, little work has examined age and strain differences in the mouse olfactory system. The present study compared the olfactory bulbs of mature (6 month) and aged (24 month) males of BALB/cBy, C57BL/6J, and DBA/2 strains. Volumes of the glomerular (GLM), external plexiform (EPL), and mitral/granule cell (MIG) layers varied little from strain to strain. Volume measurements increased with age even when corrected for body weight differences. Two nonoverlapping interneuron populations were examined with immunohistochemistry. Staining for the calcium binding protein calretinin varied little between strains, but age-related increases in staining were seen in EPL of C57BL/6J mice. Typical patterns of tyrosine hydroxylase immunoreactivity were observed in all subjects except for old DBA/2 mice, which evidenced considerable staining in submitral areas. Age-related increases were observed in BALB/cBy and DBA/2 mice but not in the C57BL/6J strain. Glial fibrillary acidic protein staining was similar in old BALB/cBy and DBA/2 mice, with astrocytes in all layers of the bulb, but more concentrated in the MIG. However, C57BL/6J tissue revealed very large astrocytes relatively evenly distributed in all layers. Cell proliferation dropped dramatically with age. Labeled cells could still be observed along the lateral ventricles, but very few were observed within the rostral migratory stream or subventricular zone. Although TUNEL labeling revealed many apoptotic figures in the granule cell layer of young subjects, almost no staining was seen in aged mice.     

Mouse strain variation in maximal electroshock seizure threshold

Maximal electroshock seizure threshold (MEST) is a classical measure of seizure sensitivity with a wide range of experimental applications. We determined MEST in nine inbred mouse strains and one congenic strain using a procedure in which mice are given one shock per day with an incremental (1 mA) current increase in each successive trial until a maximal seizure (tonic hindlimb extension) is elicited. C57BL/6J and DBA/2J mice exhibited the highest and lowest MEST, respectively, with the values of other strains falling between these two extremes. The relative rank order of MEST values by inbred strain (highest to lowest) is as follows: C57BL/6J > CBA/J = C3H/HeJ > A/J > Balb/cJ = 129/SvIMJ = 129/SvJ > AKR/J > DBA/2J. Results of experiments involving a single electroconvulsive shock given to separate groups of mice at different current intensities suggest that determination of MEST by the method used is not affected by repeated sub-maximal seizures. Overall, results document a distinctive mouse strain distribution pattern for MEST. Additionally, low within strain variability suggests that environmental factors which affect quantification of MEST are readily controlled under the conditions of this study. We conclude that MEST represents a useful tool for dissecting the multifactorial nature of seizure sensitivity in mice.     

Mouse strain differences in locomotor,sensitisation and rewarding effect of heroin; association with alterations in MOP‐r activation and dopamine transporter binding

There is growing agreement that genetic factors play an important role in the risk to develop heroin addiction, and comparisons of heroin addiction vulnerability in inbred strains of mice could provide useful information on the question of individual vulnerability to heroin addiction. This study examined the rewarding and locomotor‐stimulating effects of heroin in male C57BL/6J and DBA/2J mice. Heroin induced locomotion and sensitisation in C57BL/6J but not in DBA/2J mice. C57BL/6J mice developed conditioned place preference (CPP) to the highest doses of heroin, while DBA/2J showed CPP to only the lowest heroin doses, indicating a higher sensitivity of DBA/2J mice to the rewarding properties of heroin vs C57BL/6J mice. In order to investigate the neurobiological substrate underlying some of these differences, the effect of chronic ‘intermittent’ escalating dose heroin administration on the opioid, dopaminergic and stress systems was explored. Twofold higher μ‐opioid receptor (MOP‐r)‐stimulated [³⁵S]GTPγS binding was observed in the nucleus accumbens and caudate of saline‐treated C57BL/6J mice compared with DBA/2J. Heroin decreased MOP‐r density in brain regions of C57BL/6J mice, but not in DBA/2J. A higher density of dopamine transporters (DAT) was observed in nucleus accumbens shell and caudate of heroin‐treated DBA/2J mice compared with heroin‐treated C57BL/6J. There were no effects on D₁ and D₂ binding. Chronic heroin administration decreased corticosterone levels in both strains with no effect of strain. These results suggest that genetic differences in MOP‐r activation and DAT expression may be responsible for individual differences in vulnerability to heroin addiction.     

Genetic variance contributes to naltrexone-induced inhibition of sucrose intake in inbred and outbred mouse strains

The study of genetic variance in opioid receptor antagonism of sucrose and other forms of sweet intake has been limited to reductions in sweet intake in mice that are opioid receptor-deficient or lacking either pre-pro-enkephalin or beta-endorphin. Marked genetic variance in inbred mouse strains has been observed for sucrose intake across a wide array of concentrations in terms of sensitivity, magnitude, percentages of kilocalories consumed as sucrose and compensatory chow intake. The present study examined potential genetic variance in systemic naltrexone's dose-dependent (0.01-5 mg/kg) and time-dependent (5-120 min) ability to decrease sucrose (10%) intake in eleven inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) mouse strains. A minimum criterion sucrose intake (1 ml) under vehicle treatment, designed to avoid "floor effects" of antagonist treatment was not achieved in three (A/J, AKR/J, CBA/J) inbred mouse strains. Marked genetic variance in naltrexone's ability to inhibit sucrose intake was observed in the remaining strains with the greatest sensitivity observed in the C57BL/10J and C57BL/6J strains, intermediate sensitivity in BALB/cJ, C3H/HeJ, CD-1 and DBA/2J mice, and the least sensitivity in 129P3/J, SWR/J and SJL/J strains with a 7.5-36.5 fold range of greater effects in the ID(50) of naltrexone-induced inhibition in C57BL/10J relative to the three less-sensitive strains across the time course. Naltrexone primarily affected the maintenance, rather than the initiation of intake in BALB/cJ, CD-1, C3H/HeJ, DBA/2J and SJL/J mice, but significantly reduced sucrose intake at higher doses across the time course in C57BL/6J, C57BL/10J and 129P3/J mice. Whereas SWR/J mice failed to display any significant reduction in sucrose intake at any time point following any of the naltrexone doses, naltrexone's maximal magnitude of inhibitory effects was small (35-40%) in 129P3/J and SJL/J mice, moderate ( approximately 50%) in BALB/cJ, C3H/HeJ, CD-1 and DBA2/J mice, and profound (70-80%) in C57BL/6J and C57BL/10J mice. Indeed, the latter two strains displayed significantly greater percentages of naltrexone-induced inhibition of sucrose intake than virtually all other strains. These data indicate the importance of genetic variability in opioid modulation of sucrose intake.     

Social approach-avoidance behavior of inbred mouse strains towards DBA/2 mice

Little is known about the genetics of social approach-avoidance behaviors. We measured social approach-avoidance of prepubescent female C57BL/6J, DBA/2J, FVB/NJ, AKR/J, A/J, and BALB/cJ mice towards prepubescent DBA/2J female mice. C57BL/6J mice showed the greatest predominance of approach, while BALB/cJ mice showed the greatest predominance of avoidance. Thus, this phenotype is affected by spontaneous genetic variation in mice and can be measured in an assay useful for future neurogenetic studies.     

Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains

Three defining clinical symptoms of autism are aberrant reciprocal social interactions, deficits in social communication, and repetitive behaviors, including motor stereotypies and insistence on sameness. We developed a set of behavioral tasks designed to model components of these core symptoms in mice. Male mice from 10 inbred strains were characterized in assays for sociability, preference for social novelty, and reversal of the spatial location of the reinforcer in T-maze and Morris water maze tasks. Six strains, C57BL/6J, C57L/J, DBA/2J, FVB/NJ, C3H/HeJ, and AKR/J, showed significant levels of sociability, while A/J, BALB/cByJ, BTBR T(+)tf/J, and 129S1/SvImJ mice did not. C57BL/6J, C57L/J, DBA/2J, FVB/NJ, BALB/cByJ, and BTBR T(+)tf/J showed significant preference for social novelty, while C3H/HeJ, AKR/J, A/J, and 129S1/SvImJ did not. Normal scores on relevant control measures confirmed general health and physical abilities in all strains, ruling out artifactual explanations for social deficits. Elevated plus maze scores confirmed high anxiety-like behaviors in A/J, BALB/cByJ, and 129S1/SvImJ, which could underlie components of their low social approach. Strains that showed high levels of performance on acquisition of a T-maze task were also able to reach criterion for reversal learning. On the Morris water maze task, DBA/2J, AKR/J, BTBR T(+)tf/J, and 129S1/SvImJ failed to show significant quadrant preference during the reversal probe trial. These results highlight a dissociation between social task performance and reversal learning. BTBR T(+)tf/J is a particularly interesting strain, displaying both low social approach and resistance to change in routine on the water maze, consistent with an autism-like phenotype. Our multitask strategy for modeling symptoms of autism will be useful for investigating targeted and random gene mutations, QTLs, and microarray analyses.     

FOS and FOSB expression in the medial preoptic nucleus pars compacta of maternally active C57BL/6J and DBA/2J mice

C57BL/6J and DBA/2J inbred mice differ in aspects of maternal behavior and in the morphology of the medial preoptic nucleus (MPO), suggesting a possible association. DBA/2J mice have a compact subnucleus in the MPO, the MPOpc, that is sexually dimorphic and absent in C57BL/6J mice. To determine whether MPOpc cells are activated by maternal behavior, FOS and FOSB immunohistochemistry was performed on brain sections of C57BL/6J and DBA/2J mothers following the return of their pups after a separation of 2 days. In both light and dark phases of the daily cycle, stimulation of DBA/2J mothers evoked an increase in FOS- and FOSB-immunoreactivity in the MPOpc. Stimulated C57BL/6J mice, which lack the MPOpc, did not show an increase in cellular activity in the corresponding MPO region. Cells immediately lateral to the MPOpc were activated by pup stimulation, in both strains. These results suggest that MPOpc cells are active during maternal behavior, and that strain differences in maternal behavior are related to anatomical differences in the MPO.     

Audiogenic seizure proneness requires the contribution of two susceptibility loci in mice

Juvenile mice of the DBA/2J strain undergo generalised seizures when exposed to a high-intensity auditory stimulus. Genetic analysis identified three different loci underlying this audiogenic seizure proneness (ASP)—Asp1, Asp2 and Asp3 on chromosomes 12, 4 and 7, respectively. Asp1 is thought to have the strongest influence, and mice with only Asp1 derived from the DBA/2J strain are reported to exhibit ASP. The aim of this study was to characterise more accurately the contributions of the Asp1 and Asp3 loci in ASP using congenic strains. Each congenic strain contains a DBA/2J-derived interval encompassing either Asp1 or Asp3 on a C57BL/6J genetic background. A double congenic C57BL/6J strain containing both Asp loci derived from DBA/2J was also generated. Here, we report that DBA/2J alleles at both of these Asp loci are required to confer ASP because congenic C57BL/6 mice harbouring DBA/2J alleles at only Asp1 or Asp3 do not exhibit ASP, whereas DBA/2J alleles at both loci resulted in increased susceptibility for audiogenic seizure in double congenic C57BL/6 mice.     

Genetic diversity underlying capsaicin intake in the Mishima battery of mouse strains

Capsaicin is the active substance responsible for the pungent sensation produced by red pepper. In order to approach the underlying genetic mechanism for preference of red pepper, we conducted a 12-h, 1-bottle intake test of capsaicin solution using both male and female animals from the Mishima battery of mouse strains: 10 wild-derived inbred strains (PGN2, BFM/2, HMI, CAST/Ei, NJL, BLG2, CHD, SWN, KJR, MSM), 1 strain derived from the so-called fancy mouse (JF1), and 3 widely used laboratory strains (C57BL/6J, DBA/1J and BALB/cAnN). The concentration of capsaicin was increased from 0.5 to 15 microM successively. Gender differences were not observed in this test, but we found striking strain differences in capsaicin intake. Relative to baseline water intake, C57BL/6J and DBA/1J consumed 10%, whereas two wild strains, KJR and MSM, ingested approximately 60% of the 15-microM capsaicin solution. In a 2-bottle fluid preference test, both C57BL/6J and MSM strains reject capsaicin fluid even at the 0.5-microM concentration, which indicates that the receptors for capsaicin in these strains recognize capsaicin at a similar level. Thus, the strain differences at higher capsaicin concentrations in the 1-bottle test may reflect differences in central nervous system response to the capsaicin solution. The genetic difference in intake of capsaicin observed in these strains may provide a useful tool for identifying genes underlying response to red pepper in mice and other mammalian species.     

C57BL/6J and DBA/2J mice differ in extinction and renewal of extinguished conditioned fear

While a number of studies have examined the acquisition and expression of conditioned fear in inbred mice, very few have examined extinction of conditioned fear in inbred mice and few attempts have been made to compare extinction learning between inbred strains. Because inbred strains differ in a number of physiological and biochemical variables, differences in extinction learning may provide insight into the genetic influence of extinction learning. The purpose of this study was to examine extinction and renewal of conditioned fear in two common inbred strains of mice. C57BL/6J and DBA/2J mice were conditioned with pairings of either a tone or light and foot shock in a single session. On the following 4 days, mice were given extinction training, consisting of tone or light alone trials (Experiment 1A). C57 mice exhibited robust spontaneous recovery between sessions, but did extinguish both within and between sessions. DBA mice extinguished more quickly relative to C57 mice, and this extinction was stable between sessions (i.e., DBA mice did not exhibit spontaneous recovery). The rapid loss of fear in DBA relative to C57 mice was extinction-dependent and not merely due to poor long-term memory (Experiment 1B). Renewal testing (Experiment 2) replicated the strain difference in extinction and also showed that DBA mice have a deficit in the context specificity of extinction. C57 mice, but not DBA mice showed renewal of extinguished fear when tested in a context different from the one in which extinction training took place. These data suggest that the nature of extinction learning is influenced by characteristics of the inbred mouse strain.     

Antidepressant-like effects in various mice strains in the tail suspension test

Several studies have reported rodent strain differences in the response to antidepressants in animal models of depression. The aim of the present study was to investigate the potential contribution of genetic factors to antidepressant response in an animal model of depression: the tail suspension test (TST). For this study four mice strains (Swiss and NMRI, two outbred strains and DBA/2 and C57BL/6J Rj, two inbred strains) were submitted to the TST after acute administration of five antidepressants: the tricyclic antidepressants (TCAs) imipramine and desipramine, the selective serotonin (5-HT) reuptake inhibitors (SSRIs) paroxetine and citalopram and the dopamine reuptake inhibitor bupropion.The C57BL/6J Rj strain had a longer baseline immobility time in comparison to the other strains. All antidepressants studied in this work decreased immobility time in the Swiss and C57BL/6J Rj strains. However, the Swiss strain displayed greater sensitivity to citalopram (from 2mg/kg) and C57BL/6J Rj to paroxetine (from 0.5mg/kg). This latter presented a greater size-effect with citalopram than with other strains and reached more than 60% from 8mg/kg. Moreover the size-effect of desipramine, paroxetine and bupropion in Swiss mice was greater than in the other strains in the TST. The NMRI and DBA/2 mice only responded to 5-HT reuptake inhibitors, both selective (paroxetine, citalopram) or non-selective (imipramine). The NMRI strain was more sensitive to imipramine and presented a size-effect (43% at 8mg/kg) superior to those of other strains. DBA/2 strain was more sensitive to citalopram than paroxetine and imipramine. Our results suggest that response to an antidepressant treatment is under control of genetic factors and that the strain of mouse is an important parameter to consider.     

Morphometric analysis of obesity (ob/ob)- and diabetes (db/db)-associated hypothalamic neuronal degeneration in C57BL/KsJ mice

The influence of the obese (ob/ob) and diabetes (db/db) genetic mutations on hypothalamic structure was investigated in C57BL/KsJ and C57BL/6J mice strains by morphometric analysis of medial basal nuclei which are recognized to possess glucoregulatory neurons. Brains were collected and prepared for histomorphometric analysis at selected times following the development of expressed obesity and diabetes (Type II, non-insulin dependent) syndromes in order to compare both the strain and genomic influences on neuronal viability in the hypothalamic ventromedial (VMH) and arcuate (ARC) nuclei of mutant and age-matched control mice. The severity of each syndrome was determined by monitoring the concomitant changes in body weight and blood glucose levels in all groups. Both (db/db) and (ob/ob) mutant C57BL/KsJ mice exhibited an increase in the number and distribution of degenerated neurons in the VMH and ARC nuclei relative to corresponding controls. The mutation-associated exacerbation of the normal age-related neuronal loss, as observed in control MBH nuclei, was temporally associated with the overt expression of the hyperglycemic component of the obese and diabetes syndromes in aging C57BL/KsJ mice. No temporal or causal relationships were noted between the enhanced rate of premature neuronal degeneration, and either body weight or blood glucose levels, in either (db/db) or (ob/ob) C57BL/6J mice relative to controls. These data suggest that the hyperglycemic condition which characterizes the (ob/ob) and (db/db) mutant C57BL/KsJ mice is causally associated with the pronounced, premature MBH neuronal degeneration in these mouse strains. Neuronal changes were not pronounced when the genetic mutations were expressed in C57BL/6J mice. The accompanying alterations in brain glucose metabolism, hormone sensitivity, bioamine content and function which are recognized to occur in these mutant C57BL/KsJ mice may be causally associated consequences of the observed changes in MBH structural integrity and neuronal competence, with the severity of the mutation-associated changes being related to genetic background of the murine strain.     

GABA-gated chloride ion influx and receptor binding studies in C57BL6J and DBA2J mice

GABA-gated chloride ion influx was measured in brain 'microsac' preparations of young (20-22-day-old) and older (40-42-day-old) C57BL6J and DBA2J mice. The young DBA2J mice are susceptible to audiogenic seizures. GABA sensitivity was reduced in young DBA2J mice as compared to age-matched C57BL6J mice or older mice of either strain. Age and strain differences in ligand binding to GABA/benzodiazepine receptor complex and glutamate receptor could not account for this finding. These results provide evidence for a defect in GABA-gated chloride ion influx in audiogenic seizure-susceptible DBA2J mice.     

Finding the right motivation: genotype-dependent differences in effective reinforcements for spatial learning

Memory impairments of DBA/2J mice have been frequently reported in spatial and emotional behavior tests. However, in some memory tests involving food reward, DBA/2J mice perform equally well to C57BL/6J mice or even outperform them. Thus, it is conceivable that motivational factors differentially affect cognitive performance of different mouse strains. Therefore, spatial memory of DBA/2J and C57BL/6J mice was investigated in a modified version of the Barnes maze (mBM) test with increased complexity. The modified Barnes maze test allowed using either aversive or appetitive reinforcement, but with identical spatial cues and motor requirements. Both mouse strains acquired spatial learning in mBM tests with either reinforcement. However, DBA/2J mice learned slower than C57BL/6J mice when aversive reinforcement was used. In contrast, the two strains performed equally well when appetitive reinforcement was used. The superior performance in C57BL/6J mice in the aversive version of the mBM test was accompanied by a more frequent use of the spatial strategy. In the appetitive version of the mBM test, both strains used the spatial strategy to a similar extent. The present results demonstrate that the cognitive performance of mice depends heavily on motivational factors. Our findings underscore the importance of an effective experimental design when assessing spatial memory and challenges interpretations of impaired hippocampal function in DBA/2J mice drawn on the basis of behavior tests depending on aversive reinforcement.     

Differential involvement of the dorsal hippocampus in passive avoidance in C57bl/6J and DBA/2J mice

The inferior performance of DBA/2 mice when compared to C57BL/6 mice in hippocampus-dependent behavioral tasks including contextual fear conditioning has been attributed to impaired hippocampal function. However, DBA/2J mice have been reported to perform similarly or even better than C57BL/6J mice in the passive avoidance (PA) task that most likely also depends on hippocampal function. The apparent discrepancy in PA versus fear conditioning performance in these two strains of mice was investigated using an automated PA system. The aim was to determine whether these two mouse strains utilize different strategies involving a different contribution of hippocampal mechanisms to encode PA. C57BL/6J mice exhibited significantly longer retention latencies than DBA/2J mice when tested 24 h after training irrespective of the circadian cycle. Dorsohippocampal NMDA receptor inhibition by local injection of the selective antagonist DL-2-amino-5-phosphonovaleric acid (AP5, 3.2 microg/mouse) before training resulted in impaired PA retention in C57BL/6J but not in DBA/2J mice. Furthermore, nonreinforced pre-exposure to the PA system before training caused a latent inhibition-like reduction of retention latencies in C57BL/6J, whereas it improved PA retention in DBA/2J mice. These pre-exposure experiments facilitated the discrimination of hippocampal involvement without local pharmacological intervention. The results indicate differences in PA learning between these two strains based on a different NMDA receptor involvement in the dorsal hippocampus in this emotional learning task. We hypothesize that mouse strains can differ in their PA learning performance based on their relative ability to form associations on the basis of unisensory versus multisensory contextual/spatial cues that involve hippocampal processing.     

Dissociation of seizure traits in inbred strains of mice using the flurothyl kindling model of epileptogenesis

Previous seizure models have demonstrated genetic differences in generalized seizure threshold (GST) in inbred mice, but the genetic control of epileptogenesis is relatively unexplored. The present study examined, through analysis of inbred strains of mice, whether the seizure characteristics observed in the flurothyl kindling model are under genetic control. Eight consecutive, daily generalized seizures were induced by flurothyl in mice from five inbred strains. Following a 28-day rest period, mice were retested with flurothyl. The five strains of mice demonstrated inter-strain differences in GST, decreases in GST across seizure trials, and differences in the behavioral seizure phenotypes expressed. Since many of the seizure characteristics that we examined in the flurothyl kindling model were dissociable between C57BL/6J and DBA/2J mice, we analyzed these strains in detail. Unlike C57BL/6J mice, DBA/2J mice had a lower GST on trial 1, did not demonstrate a decrease in GST across trials, nor did they show an alteration in seizure phenotype upon flurothyl retest. Surprisingly, [C57BL/6J × DBA/2J] F1-hybrids had initial GST on trial 1 and GST decreases across trials similar to what was found for C57BL/6J, but they did not undergo the alteration in behavioral seizure phenotype that had been observed for C57BL/6J mice. Our data establish the significance of the genetic background in flurothyl-induced epileptogenesis. The [C57BL/6J × DBA/2J] F1-hybrid data demonstrate that initial GST, the decrease in GST across trials, and the change in seizure phenotype differ from the characteristics of the parental strains, suggesting that these phenotypes are controlled by independent genetic loci.     

Effect of anti-interferon-γ monoclonal antibody treatment on the development of experimental allergic encephalomyelitis in resistant mouse strains

Immunization with myelin basic protein (MBP) in complete Freund's adjuvant failed to induce experimental allergic encephalomyelitis (EAE) in six resistant mouse strains studied: A/J, BALB/c C3H/HeJ, AKR, NZW and DBA/2. However, treatment of challenged mice with anti-interferon-γ (IFN-γ) monoclonal antibody (mAb) induced severe EAE in mice of all strains except AKR. Furthermore, anti-IFN-γ mAb treatment led to increased disease incidence and severity in BALB/c mice challenged with the MBP peptide_87–103, known to be encephalitogenic for the susceptible SJL strain. In three strains tested, anti-IFN-γ mAb enhanced passively induced EAE in the A/J and C3H/HeJ but not in the BAlB/c mice. All mice with clinically overt EAE had widespread histological lesions characterized by mononuclear cell infiltrates and focal demyelination. The results indicate that resistant strains are genetically capable of developing EAE, and that IFN-γ can contribute to disease resistance.     

Simultaneous olfactory discrimination elicits a strain-specific increase in dendritic spines in the hippocampus of inbred mice

This study examines the extent to which simultaneous olfactory discrimination learning increases spine density on hippocampal CA1 pyramidal neurons in C57BL/6J (C57) and DBA/2J (DBA) inbred mice, characterized by spontaneous differences in hippocampal plasticity and hippocampus-related learning. The behavioral data first showed a clear-cut difference in performance between the two strains. C57 mice learned to identify the positively reinforced olfactory cue whereas DBA did not. Both strains, however, similarly acquired the procedural aspects of the task. The morphological analysis performed 24 h post-training revealed that spine density was significantly increased along apical, oblique, and basal dendrites in trained C57 mice compared to trained DBA mice, and to pseudotrained as well as to control cage mice of both strains. These findings confirm the ability of C57 mice to solve hippocampal-dependent tasks and provide the first evidence that simultaneous olfactory discrimination learning elicits spine growth in the mouse hippocampus. In addition, the finding that DBA mice failed to discriminate between the two olfactory cues but were as efficient as C57 mice in learning the procedural aspects of the task outlines that the structural changes observed in the latter strain were independent from any procedural learning component.     

Synaptic plasticity in the hippocampus of awake C57BL/6 and DBA/2 mice: interstrain differences and parallels with behavior.

C57BL/6 mice consistently outperform DBA/2 mice in a range of hippocampal-dependent spatial learning behaviors. We recorded evoked responses from the dentate gyrus of awake, freely-moving mice and measured synaptic plasticity (LTP) and performance in a hippocampal-dependent task in individual animals from these two inbred strains. Spatial alternation tasks confirmed the behavioral divergence between the two strains, with C57BL/6 mice demonstrating more robust alternation than DBA/2 mice. Recording changes in field potentials in the dentate gyrus following three different high-frequency stimulation paradigms in the same groups of animals revealed differences in neural plasticity: both strains were able to support long-term potentiation (LTP) at perforant path synapses, but brief high-frequency stimulation induced larger and longer potentiation of the population spike in C57BL/6 than in DBA/2 mice. This greater propensity for population-spike potentiation in the strain that performed better in a hippocampal-dependent task is in accord with the different neurochemical profiles of C57BL/6 and DBA/2 mice.