The behavioral neurobiology of learning and memory: A conceptual reorientation

Research on the neurobiology of learning and memory has been guided by two major theories: (i) memory as a psychological process and (ii) memory as a change in synaptic neural connectivity. It is not widely recognised that not only are these theories different but, moreover, they are fundamentally incompatible. Confusion concerning basic concepts in the learning and memory field in mammals has lead to the creation of an extensive but often inconclusive experimental literature. However, one important conclusion suggested by recent work in this field is that experience-dependent changes in neural connectivity occur in many different brain systems. Particular brain structures, such as the hippocampus, do not play any uniquely important role in experience-dependent behavior. Research in learning and memory can be best pursued on the basis of biological studies of animal behavior and a cellular approach to brain function.     

Pretreatment with aldosterone or corticosterone blocks the memory-enhancing effects of nimodipine,captopril, CGP 37 849, and strychnine in mice

Oral pretreatment with aldosterone or corticosterone blocked the memory-enhancing effects of the calcium antagonist nimodipine, the ACE inhibitor captopril, the NMDA blocker CGP 37 849, and the glycine antagonist strychnine in a passive-avoidance test in mice. The memory-disturbing effects of phenobarbitone, diazepam, CGP 37 849 and scopolamine were not influenced by the hormonal pretreatment. These findings could indicate the involvement of a steroid-sensitive mechanism in drug-induced improvement of memory. In the light of clinical observations showing elevated cortisol levels in Alzheimer patients, the results might also explain why only a limited number of these patients respond to therapy with memory enhancers.     

Investigations of neurotoxicity and neuroprotection within the nucleus basalis of the rat

The present study investigated the specific ways by which cytotoxicity due to glutamate receptor stimulation could be attenuated by the administration of agonists and antagonists of the ionotropic and metabotropic glutamate receptors within the nucleus basalis magnocellularis (NBM) of rats as measured by cortical choline acetyltransferase activity. The results of these studies suggest that (1) the cytotoxicity of ibotenate to NBM cholinergic cells is not dependent upon stimulation of metabotropic glutamate receptors, but results from activation of (NMDA) receptors, (2) the cytotoxicity of quisqualate to cholinergic cells within the NBM is not dependent upon stimulation of NMDA or metabotropic receptors, and (3) the cytotoxicity of NMDA was prevented by administration (i.p.) of the un-competitive NMDA antagonist memantine (30 mg/kg), resulting in plasma levels of 2.5 μg/ml, a concentration known to block efficiently NMDA receptors in vitro. Finally, performance of a food-motivated, delayed-alternation task on a T-maze was impaired by injections of NMDA into the NBM, but was prevented by co-administration of NMDA with memantine.     

Behavioral dissociation of anterodorsal and posteroventral hippocampus by subseizure stimulation in mice

BALB/c mice were bilaterally implanted with bipolar electrodes either in anterodorsal (ADH) or posteroventral hippocampus (PVH) in order to compare the effects of postsession electrical stimulation on memory processes. For each experiment, 30 s after the end of the first session, the animals were stimulated during 80 s. For both hippocampal regions, the stimulation intensity was half of the afterdischarge threshold value. Control groups were naive, ADH and PVH implanted non-stimulated animals. Different appetitive and aversive tasks were used. Subseizure stimulation never created a deficit. Depending on the region of the hippocampus stimulated and on the learning task, a retention enhancement was eventually observed. These data are in agreement with the involvement of hippocampus in initial stages of memory consolidation. Further, the subseizure stimulation permitted a functional dissociation between the two hippocampal regions. Both regions seemed involved in the integration of information, but the anterodorsal part would be rather related to behavioral inhibition, while the posteroventral part would have the capacity to induce an arousal state allowing behavioral flexibility.     

Neural plasticity in vivo: opioid sensitivity of memory develops gradually after a septal lesion

Neuronal plasticity can manifest itself in alterations in the sensitivity of memory to the effects of drugs. After the production of a brain lesion, the memory processing of a passive-avoidance task in mice gradually becomes sensitive to the effect of morphine, i.e., an improvement in retention performance is seen after 6 weeks, but not after 1 or 2 weeks. The results presented demonstrate that, even if they lead to no discernible changes in behaviour, plastic processes can still be detected by means of behavioural tests.     

低强度超短波对小鼠体质及智力的影响

本实验探讨了低强度超短波对小鼠连续三代辐射,对学习、记忆、拉力、运动耐力和周围血象的影响。用81MHz,10～12V/m 的超短波进行辐射,每天辐射2小时,每周6天。结果表明:经过超短波辐射的各代小鼠与对照组相比,学习能力、记忆能力、拉力及运动耐力有明显的降低,且运动耐力有进行性降低的趋势,而经过辐射的三代小鼠红细胞、血红蛋白含量及白细胞数均明显增高,每个红细胞的血红蛋白含量则低于对照组。     

认知矫正治疗前后慢性精神分裂症患者功能磁共振成像的对照研究

目的 探讨认知矫正治疗对精神分裂症患者工作记忆相关脑区活动的影响.方法 对10例病情稳定的慢性精神分裂症患者进行为期6个月的认知矫正治疗,分别于治疗前后进行韦克斯勒记忆量表(WMS)测查及功能磁共振成像(fMRI)测量.结果 (1)WMS测查:治疗后再认[(8.11±4.34)分]和再生[(10.22±3.35)分]以及Benton错误[(3.75±2.92)分]均较治疗前[分别为(5.78±2.95)分、(8.56±3.21)分和(8.00±6.28)分]改善,均P＜0.05.(2)fMRI:治疗前后的反应时和正确率比较,差异无统计学意义(P＞0.05).治疗后在高负荷条件下,背侧前额叶皮质(DLPFC)区域(Brodmann46区)的激活范围(x,y,z=-51,36,15;k=40,t=7.21)小于治疗前的激活范围(x,y,z=-48,24,24,k=154,t=12.72),治疗前后DLPFC区域激活(x,y,z=-24,36,18,k=12,t=3.75)的差异有统计学意义(P＜0.005);在低负荷条件下,治疗前后DLPFC区域激活的差异无统计学意义(P＞0.05).结论 认知矫正治疗能改善精神分裂症患者工作记忆相关脑区的活动.     

Effects of purine analogues on spontaneous alternation in mice

The Y-maze was used to examine the effects of purines acting at A₁ and A₂ adenosine receptors upon spontaneous alternation, a model of working memory, in mice. In support of previous work, scopolamine produced a loss of spontaneous alternation behaviour to the 0.5 chance level. The A₁ receptor selective agonist N6-cyclopentyladenosine (CPA) did not change spontaneous alternation behaviour alone, but it prevented the decrease of spontaneous alternation scores produced by scopolamine. The A₁ receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (CPX) blocked the effect of CPA in combination with scopolamine but had no effect alone. The A₂ receptor selective agonist (N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), and the A₂ receptor selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect of alternation behaviour alone and did not modify the effect of scopolamine. The results indicate the ability of A₁ but not A₂ receptor activation to modify working memory deficits induced by scopolamine, but suggest that endogenous adenosine does not normally participate in working memory processes.     

A comparison of the effects of scopolamine and diazepam on acquisition and retention of inhibitory avoidance in mice

Administration of either the muscarinic antagonist scopolamine or the benzodiazepine diazepam prior to training produced a dose-dependent impairment in the retention of one-trial inhibitory avoidance training in mice. To investigate the nature of this drug effect, the effects of scopolamine and diazepam were subsequently assessed on both acquisition and retention of inhibitory avoidance using a multiple-trial, training-to-criterion procedure. The training was conducted using either continuous trials in which the mouse was free to shuttle back and forth between shock and safe compartments or discrete trials in which the mouse was moved from the shock compartment of the safe compartment at the start of each trial. In either case, training continued until the mouse refrained from crossing into the shock compartment for a specified length of time on a single trial. Scopolamine (1.0 mg/kg) administered before training significantly increased the number of trials required to attain criterion, but did not affect retention when these mice were tested 2, 16, or 28 days later. In contrast, diazepam (1.0 mg/kg) did not significantly alter the number of trials necessary to reach criterion, but impaired retention of the inhibitory response in mice trained using discrete trials. The differences in the amnestic effects of scopolamine and diazepam revealed by this detailed analysis suggest that diazepam does not impair inhibitory avoidance performance through an effect on cholinergic function.     

Patients with heart attacks are not valid models for medial temporal lobe amnesia. A neuropsychological and FDG-PET study with consequences for memory research

Equating the condition after cardiac arrest with that of medial temporal damage, and consequently medial temporal lobe amnesia, is questioned on the basis of results from a patient who was studied neuropsychologically as well as with static and dynamic imaging methods (MRI, PET) 6–9 months after a heart attack. The patient manifested severe and persistent anterograde and retrograde amnesia, as well as further cognitive deteriorations. While MRI only indicated non-specific cortical atrophy, PET revealed a severe bilateral affection of the thalamus and of both medial and lateral temporal cortices as well as occipito-parietal hypometabolism. The neuropsychological status indicates that patients with a diagnosis of cardiac arrest may suffer very severe and persistent cognitive deficits; the imaging analyses show that cardiac arrests may lead to quite severe and widespread brain damage which, however, may not be visible with current magnetic resonance imaging technology, but which is clearly apparent from positron emission tomography. These data suggest that patients with a condition after a heart attack may not be valid models for pure hippocampal—or even medial temporal lobe—pathology, as they may suffer much more widespread brain damage.