Deep Brain Stimulation of the Medial Septal Area Can Modulate Gene Expression in the Hippocampus of Rats under Urethane Anesthesia

We studied the effects of stimulation of the medial septal area on the gene expression in the dorsal and ventral hippocampus. Rats under urethane anesthesia were implanted with a recording electrode in the right hippocampus and stimulating electrode in the dorsal medial septum (dMS) or medial septal nucleus (MSN). After one-hour-long deep brain stimulation, we collected ipsi- and contralateral dorsal and ventral hippocampi. Quantitative PCR showed that deep brain stimulation did not cause any changes in the intact contralateral dorsal and ventral hippocampi. A comparison of ipsi- and contralateral hippocampi in the control unstimulated animals showed that electrode implantation in the ipsilateral dorsal hippocampus led to a dramatic increase in the expression of immediate early genes (c-fos, arc, egr1, npas4), neurotrophins (ngf, bdnf) and inflammatory cytokines (il1b and tnf, but not il6) not only in the area close to implantation site but also in the ventral hippocampus. Moreover, the stimulation of MSN but not dMS further increased the expression of c-fos, egr1, npas4, bdnf, and tnf in the ipsilateral ventral but not dorsal hippocampus. Our data suggest that the activation of medial septal nucleus can change the gene expression in ventral hippocampal cells after their priming by other stimuli.     

血管性痴呆小鼠海马神经元超微病理特征研究

目的：探讨血管性痴呆(VD)小鼠海马神经元超微病理特征及其变化的意义。方法：采用双侧颈总动脉线结、反复缺血—再灌注法,制作小鼠VD动物模型。取两组小鼠海马组织制成超薄切片,透射电镜观察。结果：(1)假手术组：海马神经元和神经毡结构均正常。(2)VD模型组：海马神经元核肿胀、有局部凹陷现象;核周体细胞器明显减少,多聚核糖体稀散;仅残留受到破坏的高尔基体和粗面内质网、线粒体变性。髓鞘层裂;轴突中神经微管结构模糊。神经毡中可见树突和轴突不同程度水肿,尤其是树突呈现极度扩张形成不规则的“气球”,其中含有许多大小不等的薄膜空泡。突触数量显著减少,可见穿孔和异形的突触;有的突触小泡破裂,呈片状均质化。结论：海马神经元的超微结构病变导致神经元功能异常、突触可塑性降低,可能在VD的病因中起重要作用。     

Further Evidence of the Melatonin Calmodulin Interaction: Effect on CaMKII Activity

Melatonin (MEL) is a pleiotropic indolamine that reaches multiple intracellular targets. Among these, MEL binds to calmodulin (CaM) with high affinity. In presence of Ca²⁺, CaM binds to CaM-dependent kinase II (CaMKII). The Ca²⁺-CaM/CaMKII pathway regulates a myriad of brain functions in different cellular compartments. Evidence showing the regulation of this cellular pathway by MEL is scarce. Thus, our main objective was to study the interaction of MEL with CaM and its effects on CaMKII activity in two microenvironments (aqueous and lipidic) naturally occurring within the cell. In addition, colocalization of MEL with CaM in vivo was explored in mice brain hippocampus. In vitro CaM-MEL interaction and the structural conformations of CaM in the presence of this indoleamine were assessed through electrophoretic mobility and isoelectric point. The functional consequence of this interaction was evaluated by measuring CaMKII activity. Ca²⁺-CaM-MEL increased the activity of CaMKII in aqueous buffer but reduced the kinase activity in lipid buffer. Importantly, MEL colocalizes in vivo with Ca²⁺-CaM in the hippocampus. Our evidence suggests that MEL regulates the key cellular Ca²⁺-CaM/CaMKII pathway and might explain why physiological MEL concentrations reduce CaMKII activity in some experimental conditions, while in others it drives biological processes through activation of this kinase.     

The sea horse comes of age: Theoretical comment on Rehbein, Killiany, and Mahut (2005) and Killiany, Rehbein, and Mahut (2005).

Impairments in various aspects of learning and memory have been ascribed to the effects of damage to the hippocampal formation in adult nonhuman primates. Whether these effects reflect disturbance of a unitary process or multiple processes within the hippocampus and whether other systems may participate in these functions is unclear. After making hippocampal ablations in infant rhesus monkeys (Macaca mulatta), L. Rehbein, R. Killiany, and H. Mahut (2005) (see record 2005-06959-001) and R. Killiany, L. Rehbein, and H. Mahut (2005) (see record 2005-06959-002) reported a dissociation of effect between tasks of recognition memory and contextual retrieval (impaired) and associative learning (spared). The findings point to an ontogenetic dissociation of function within the hippocampal formation and, at the same time, support the view of the coexistence of at least two neural systems that underlie memory and learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Androgen deprivation impairs memory in older men.

Androgen deprivation leads to a profound loss of synaptic density in the hippocampus and changes in learning and memory in animal models. The authors examined group differences in verbal memory between men on androgen deprivation therapy (ADT), a commonly used treatment for prostate cancer, and healthy men. The authors found that men on ADT have a specific impairment of retention but normal encoding and retrieval processes on a word list-learning task. Speed and accuracy for both perceptual and semantic encoding, as well as retrieval at a very short retention interval, were not affected; however, recognition fell to chance after a 2-min retention interval in men on ADT. Healthy men showed only moderate forgetting, and performance was still above chance at 12 min. This pattern of preserved encoding and retrieval but impaired retention suggests that androgens play a role in hippocampally mediated memory processes, possibly having a specific affect on consolidation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed development of place navigation compared to directional responding in young rats.

Recent work from our laboratory demonstrates that both young and adult rats show a preference for directional responding over place navigation in the Morris water task. Based on these findings, previous studies on the postnatal development of spatial learning have most likely assessed the ontogeny of directional responding instead of true place navigation. Here, we examined the development of directional responding and place navigation among young male and female rats using two variants of the Morris water task that specifically require directional and place responses. In the place variant, the hidden platform remained in the same absolute spatial location regardless of pool position. In the direction variant, the platform remained in the same direction in the room regardless of pool position. We found that ability to solve the direction task emerged around 20 to 21 days of age, whereas ability to solve the place task did not emerge until 26 to 27 days of age. These findings indicate that directional responding and place navigation exhibit different developmental trajectories and suggest that the 2 forms of navigation have different neurobiological bases. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

M-type potassium conductance controls the emergence of neural phase codes: a combined experimental and neuron modelling study

Rate and phase codes are believed to be important in neural information processing. Hippocampal place cells provide a good example where both coding schemes coexist during spatial information processing. Spike rate increases in the place field, whereas spike phase precesses relative to the ongoing theta oscillation. However, what intrinsic mechanism allows for a single neuron to generate spike output patterns that contain both neural codes is unknown. Using dynamic clamp, we simulate an in vivo-like subthreshold dynamics of place cells to in vitro CA1 pyramidal neurons to establish an in vitro model of spike phase precession. Using this in vitro model, we show that membrane potential oscillation (MPO) dynamics is important in the emergence of spike phase codes: blocking the slowly activating, non-inactivating K⁺ current (I_M), which is known to control subthreshold MPO, disrupts MPO and abolishes spike phase precession. We verify the importance of adaptive I_M in the generation of phase codes using both an adaptive integrate-and-fire and a Hodgkin–Huxley (HH) neuron model. Especially, using the HH model, we further show that it is the perisomatically located I_M with slow activation kinetics that is crucial for the generation of phase codes. These results suggest an important functional role of I_M in single neuron computation, where I_M serves as an intrinsic mechanism allowing for dual rate and phase coding in single neurons.     

Modeling hippocampal and neocortical contributions to recognition memory: A complementary-learning-systems approach.

The authors present a computational neural-network model of how the hippocampus and medial temporal lobe cortex (MTLC) contribute to recognition memory. The hippocampal component contributes by recalling studied details. The MTLC component cannot support recall, but one can extract a scalar familiarity signal from MTLC that tracks how well a test item matches studied items. The authors present simulations that establish key differences in the operating characteristics of the hippocampal-recall and MTLC-familiarity signals and identify several manipulations (e.g., target-lure similarity, interference) that differentially affect the 2 signals. They also use the model to address the stochastic relationship between recall and familiarity and the effects of partial versus complete hippocampal lesions on recognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anatomical and behavioral analysis of hippocampal cell fields in rats

For a study of the structure and function of the different hippocampal cell fields, a surgical approach was devised that permitted selective damage to either the hippocampal subdivisions or the major efferent projections. Neuroanatomical techniques were used in Experiment 1 to verify the selective nature of the lesions and to provide information concerning differential hippocampal projections. In Experiment, 2, rats with selective hippocampal lesions were tested on a series of tasks chosen to measure various aspects of behavior. Animals with fimbrial lesions interrupting connections between the CA3-CA4 cell fields and the septal region were similar to animals with extensive hippocampal lesions in being more active than the other groups at night, more active during the day, and more affected by deprivation. In addition, both groups were facilitated in acquisition of a shuttle box avoidance task. Extensive damage to the hippocampus and more selective damage to the CA1 pyramidal cell field resulted in impaired spatial reversal learning. The results are interpreted as providing support for the view that the two main subdivisions of the hippocampus, the CA1 and CA3-CA4 cell fields, are differentially involved in behavior.     

Effects of ethanol on encoding, consolidation, and expression of extinction following contextual fear conditioning.

Studies of contextual fear conditioning have found that ethanol administered prior to a conditioning session impairs the conditioned freezing response during a test session the next day. The present experiments examined the effects of ethanol on extinction, the loss of conditioned responding that occurs as the animal learns that a previously conditioned context no longer signals shock. Ethanol (1.5 g/kg) administered prior to single (Experiment 1) or multiple (Experiment 2) extinction sessions impaired extinction. Ethanol administered prior to a test session disrupted the expression of freezing after extinction (Experiments 3-5). There was some evidence that ethanol served as an internal stimulus signaling the operation of conditioning or extinction contingencies (Experiments 4-5). In Experiment 6, postsession injections of 1.5 g/kg ethanol had no effect on extinction with brief (3 min) or long (24 min) exposures to the context, but injections of 3 g/kg after long exposures impaired extinction. Together, these results indicate that ethanol affects extinction by acting on multiple learning and performance processes, including attention, memory encoding, and memory expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)