GABAergic interneuron migration and the evolution of the neocortex

A neocortex is present in all mammals but is not present in other classes of vertebrates, and the neocortex is extremely elaborate in humans. Changes in excitatory projection neurons and their progenitors within the developing dorsal pallium in the most recent common ancestor of mammals are thought to have been involved in the evolution of the neocortex. Our recent findings suggest that changes in the migratory ability of inhibitory interneurons derived from outside the neocortex may also have been involved in the evolution of the neocortex. In this article we review the literature on the migratory profile of inhibitory interneurons in several different species and the literature on comparisons between the intrinsic migratory ability of interneurons derived from different species. Finally, we propose a hypothesis about the mammalian-specific evolution of the migratory ability of interneurons and its potential contribution to the establishment of a functional neocortex.     

Photoperiod controls the induction,retention, and retrieval of antigen-specific immunological memory

Changes in day length affect several measures of immunity in seasonally breeding mammals. In Siberian hamsters (Phodopus sungorus), short day lengths suppress specific secondary antibody responses to the keyhole limpet hemocyanin (KLH) antigen and enhance cutaneous delayed-type hypersensitivity (DTH) responses to dinitrofluorobenzene (DNFB). These experiments tested whether day length affects secondary antibody and DTH responses by altering immune function solely during the interval after the initial exposure to each antigen, solely during the interval after the second exposure, or during both stages of the respective immune responses. Adult male Siberian hamsters were exposed to either a long (16 h light/day; LD) or a short (8 h light/day; SD) photoperiod for 7.5 wk before receiving an initial exposure to each antigen (KLH injection, cutaneous DNFB treatment; separate groups of animals for each antigen). A subset of LD hamsters was transferred to the SD photo-period, and a subset of SD hamsters was transferred to the LD photoperiod. Other hamsters remained in LD or SD. Eight weeks later, all hamsters were challenged with a second subcutaneous injection of KLH or a second application of DNFB to the ear, and immune responses were measured. Exposure to SD during the primary antibody response did not affect secondary IgG responses, but SD exposure during the secondary response significantly suppressed IgG production independent of day length during the initial KLH treatment. In contrast, exposure to SD during the DNFB challenge enhanced the ensuing DTH response, but this enhancement depended on the photoperiod prevailing during the initial exposure. Exposure to SD during the sensitization stage did not enhance DTH in hamsters subsequently exposed to LD. The data suggest that short photoperiods have enduring effects on immune responsiveness and on the establishment and retention of immunological memory.     

Parvalbumin interneuron inhibition onto anterior insula neurons projecting to the basolateral amygdala drives aversive taste memory retrieval

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Glia-derived D-serine controls NMDA receptor activity and synaptic memory

The NMDA receptor is a key player in excitatory transmission and synaptic plasticity in the central nervous system. Its activation requires the binding of both glutamate and a co-agonist like D-serine to its glycine site. As D-serine is released exclusively by astrocytes, we studied the physiological impact of the glial environment on NMDA receptor-dependent activity and plasticity. To this end, we took advantage of the changing astrocytic ensheathing of neurons occurring in the supraoptic nucleus during lactation. We provide direct evidence that in this hypothalamic structure the endogenous co-agonist of NMDA receptors is D-serine and not glycine. Consequently, the degree of astrocytic coverage of neurons governs the level of glycine site occupancy on the NMDA receptor, thereby affecting their availability for activation and thus the activity dependence of long-term synaptic changes. Such a contribution of astrocytes to synaptic metaplasticity fuels the emerging concept that astrocytes are dynamic partners of brain signaling.     

Glutamatergic and GABAergic effects of fipronil on olfactory learning and memory in the honeybee

We investigated here the role of transmissions mediated by GABA and glutamate-gated chloride channels (GluCls) in olfactory learning and memory in honeybees, both of these channels being a target for fipronil. To do so, we combined olfactory conditioning with injections of either the GABA- and glutamate-interfering fipronil alone, or in combination with the blocker of glutamate transporter l-trans-Pyrrolidine-2,4-Dicarboxylicacid (l -trans-PDC), or the GABA analog Trans-4-Aminocrotonic Acid (TACA). Our results show that a low dose of fipronil (0.1 ng/bee) impaired olfactory memory, while a higher dose (0.5 ng/bee) had no effect. The detrimental effect induced by the low dose of fipronil was rescued by the coinjection of l-trans-PDC but was rather increased by the coinjection of TACA. Moreover, using whole-cell patch-clamp recordings, we observed that l-trans-PDC reduced glutamate-induced chloride currents in antennal lobe cells. We interpret these results as reflecting the involvement of both GluCl and GABA receptors in the impairment of olfactory memory induced by fipronil.     

The effect of intrahippocampal insulin microinjection on spatial learning and memory

Insulin is best known for its action on peripheral target tissues such as the adipocyte, muscle and liver to regulate glucose homeostasis. Insulin and its receptor are found in specific area of CNS with a variety of region-specific functions different from its direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions. Previous studies about the effect of insulin on memory are controversial. In the present study, the effect of insulin microinjection into CA1 region of rat hippocampus on water maze performance has been investigated. Insulin had a discrepant effect dose dependently. The spatial learning and memory were impaired with lower dose of insulin, had not changed with intermediate doses, while they improved with higher doses. These results suggest that insulin may have a dose-dependent effect on spatial learning and memory.     

Hippocampal polyamine levels and transglutaminase activity are paralleling spatial memory retrieval in the C57BL/6J mouse

Although a potential role for polyamines and transglutaminases (TGs) in memory mechanisms have been proposed, hippocampal spermine (SPM) and spermidine (SPD) levels as well as transamidating activity of TG in spatial memory have not been addressed yet. It was therefore the aim of the study to assess hippocampal polyamines and TG activity at the probe trial in a spatial memory paradigm. C57BL/6J mice (20 animals per group) were used for the experiments and divided into a trained and a yoked (untrained) group. The Morris water maze (MWM) was selected as the memory test, animals were sacrificed within 5 min following the probe trial and hippocampi were taken for biochemical analysis. SPD and SPM levels were assessed by an analytical procedure according to Gismondi et al. Transamidating activity of TG was determined following the method described by Chung and Folk using [14C] methylamine as substrate. γ-(Glutamyl)-polyamine levels were evaluated by ion exchange chromatography according to Folk et al. Animals learned the task in the MWM as latencies and pathlengths were significantly reduced. At the probe trial mice showed significantly higher preference for the target quadrant. Free SPD and SPM levels were manifold decreased in the trained as compared to the yoked group. Transamidating activity of TG was fourfold increased in trained as compared to yoked controls. γ-(Glutamyl)-SPD was comparable while γ-(glutamyl)-SPM was significantly higher in the trained group. The findings show a potential role for polyamines, their derivative γ-(glutamyl)-SPM and transamidating activity of TG at memory retrieval or formation. Results from this study are extending and knowledge on polyamines and report for the first time involvement of γ-(glutamyl)-SPM and transamidating activity of TG that may form the basis for future neurochemical and pharmacological studies and indeed, modulation of polyamine and TG activity has been already proposed as a tentative therapeutical concept.     

Effects of testosterone on spatial learning and memory in adult male rats

A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting 7 days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects.     

褪黑素对大鼠空间学习记忆的影响及其机制研究

本研究运用Morris水迷宫和电生理学方法 ,以逃避潜伏期、穿环系数和海马CA1区突触长时程增强(long termpotentiation ,LTP)为指标 ,研究褪黑素对大鼠空间学习记忆能力的影响。实验结果显示 :( 1)在Morris水迷宫 6d训练中 ,对照组大鼠后 4d平均逃避潜伏期为 18 4 4± 2 7s,褪黑素组为 3 0 0 2± 3 6s,两者有显著差异 (P <0 0 1) ;训练 6d后 ,褪黑素组穿环系数为 2 5 68± 2 3 2 % ,明显小于对照组的 4 3 3 3± 2 85 % (P <0 0 1)。( 2 )采用微量注射法给予海马CA1区褪黑素 ,强直后 60min ,fEPSP斜率为基准值的 114 2 8± 1 80 % ,显著低于对照组的 169 71±6 4 8% (P <0 0 1)。( 3 )预先给予东莨菪碱 ,不影响褪黑素对海马CA1区LTP的抑制 ,强直后 60minfEPSP斜率为基准值的 113 70± 5 5 5 %。( 4 )提前给予荷包牡丹碱后给予褪黑素 ,强直后 60minfEPSP斜率为基准值的 162 2 9±10 5 2 % ,明显大于褪黑素组 (P <0 0 1) ,而与对照组无显著差异 (P >0 0 5 )。上述结果表明 ,褪黑素对大鼠的空间学习记忆能力及海马CA1区LTP均有明显的抑制作用 ,两者相关 ;东莨菪碱不能阻断褪黑素对海马CA1区LTP的抑制作用 ,而荷包牡丹碱可以阻断褪黑素对LTP的抑制 ,提示褪黑素的作用可能不是由胆碱能系统所介     

Effect of quercetin on chronic enhancement of spatial learning and memory of mice

In this study we evaluated the effect of quercetin on D-galactose-induced aged mice using the Morris water maze (MWM) test. Based on the free radical theory of aging, experiments were performed to study the possible biochemical mechanisms of glutathione (GSH) level and hydroxyl radical (OH⁻) in the hippocampus and cerebral cortex and the brain tissue enzyme activity of the mice. The results indicated that quercetin can enhance the exploratory behavior, spatial learning and memory of the mice. The effects relate with enhancing the brain functions and inhibiting oxidative stress by quercetin, and relate with increasing the GSH level and decreasing the OH⁻ content. These findings suggest that quercetin can work as a possible natural anti-aging pharmaceutical product.     

Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory

The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory.     

Morris water maze: procedures for assessing spatial and related forms of learning and memory

The Morris water maze (MWM) is a test of spatial learning for rodents that relies on distal cues to navigate from start locations around the perimeter of an open swimming arena to locate a submerged escape platform. Spatial learning is assessed across repeated trials and reference memory is determined by preference for the platform area when the platform is absent. Reversal and shift trials enhance the detection of spatial impairments. Trial-dependent, latent and discrimination learning can be assessed using modifications of the basic protocol. Search-to-platform area determines the degree of reliance on spatial versus non-spatial strategies. Cued trials determine whether performance factors that are unrelated to place learning are present. Escape from water is relatively immune from activity or body mass differences, making it ideal for many experimental models. The MWM has proven to be a robust and reliable test that is strongly correlated with hippocampal synaptic plasticity and NMDA receptor function. We present protocols for performing variants of the MWM test, from which results can be obtained from individual animals in as few as 6 days.     

Impairment of hippocampal long-term depression and defective spatial learning and memory in p35 mice

Cdk5 (cyclin-dependent kinase 5) activity is dependent upon association with one of two neuron-specific activators, p35 or p39. Genetic deletion of Cdk5 causes perinatal lethality with severe defects in corticogenesis and neuronal positioning. p35(-/-) mice are viable with milder histological abnormalities. Although substantial evidence implicates Cdk5 in synaptic plasticity, its role in learning and memory has not been evaluated using mutant mouse models. We report here that p35(-/-) mice have deficiencies in spatial learning and memory. Close examination of hippocampal circuitry revealed subtle histological defects in CA1 pyramidal cells. Furthermore, p35(-/-) mice exhibit impaired long-term depression and depotentiation of long-term potentiation in the Schaeffer collateral CA1 pathway. Moreover, the Cdk5-dependent phosphorylation state of protein phosphatase inhibitor-1 was increased in 4-week-old mice due to increased levels of p39, which co-localized with inhibitor-1 and Cdk5 in the cytoplasm. These results demonstrate that p35-dependent Cdk5 activity is important to learning and synaptic plasticity. Deletion of p35 may shift the substrate specificity of Cdk5 due to compensatory expression of p39.     

The effects of the neurotoxin DSP4 on spatial learning and memory in Wistar rats

The aim of the present study was to investigate the effect of DSP4-induced noradrenaline depletion on learning and memory in a spatial memory paradigm (holeboard). Since Harro et al. Brain Res 976:209-216 (2003) have demonstrated that short-term effects of DSP4 administration include both noradrenaline depletion and changes in dopamine and its metabolites-with the latter vanishing within 4 weeks after the neurotoxic lesion-the behavioural effects observed immediately after DSP4 administration cannot solely be related to noradrenaline. In the present study, spatial learning, reference memory and working memory were therefore assessed 5-10 weeks after DSP4 administration. Our results suggest that the administration of DSP4 did not lead to changes in spatial learning and memory when behavioural assessment was performed after a minimum of 5 weeks following DSP4. This lack of changes in spatial behaviour suggests that the role of noradrenaline regarding these functions may be limited. Future studies will therefore have to take into account the time-course of neurotransmitter alterations and behavioural changes following DSP4 administration.     

Showercap Mindmap: a spatial activity for learning physiology terminology and location

Students struggle with the volume and complexity of physiology terminology. We compared first-year undergraduate psychology students' learning of physiological terms using two teaching methods: one verbal (control group; n = 16) and one spatial and multisensory (experimental group; n = 19). The experimental group used clear plastic shower caps to mark brain regions and affix labels to another participant's head. The control group learned the material verbally through a game. When tested verbally, both the control and experimental groups recalled more of the 10 terms immediately after the activity (+106% and +83%, respectively) and 2 wk later (+53% and +31%, respectively) than at the pretest (P < 0.0005). When participants' knowledge was tested spatially (labeling a brain diagram), the experimental group recalled more terms at the posttest (+76%) and followup (+73%) than at the pretest (P < 0.0005), but the control group who showed no improvement at either time point (+12% and +14%, respectively). These findings support the notion that spatial and multisensory learning produces improved spatial recall over time while also supporting the notion of transfer-appropriate processing.