Epinephrine modulates memory of latent learning in an inhibitory avoidance task.

The present study examined the memory modulatory effect of epinephrine on latent learning of an inhibitory avoidance task. Male Sprague-Dawley rats on the first day were subjected to one of three conditions (no, short or long) in pre-exposure to the task apparatus. One day or several days later, they received the typical inhibitory avoidance training with a 0.5 mA/0.5 s foot shock. Memory of the inhibitory avoidance response was tested one day after the foot-shock training. The long pre-exposure group showed better memory than the no or short pre-exposure group, and this latent memory could last for 6 days: Retention scores of the long pre-exposure group were significantly better than those of the no pre-exposure group if the shock training was given 3 or 6 days, but not 12 or 21 days, after the pre-exposure. Epinephrine injected after the pre-exposure training modulated the latent memory in a dose- and time-dependent manner: 0.01 mg/kg given shortly after the short pre-exposure enhanced the memory, but 0.5 mg/kg given shortly after the long pre-exposure impaired it. Epinephrine injected 4 h after the pre-exposure had no effect, neither did that given to rats pre-exposed to a different context. Epinephrine (0.01 mg/kg) also made the latent memory lasting longer as the rats treated with it showed significant avoidance behavior when they had the shock training at 12 or 21 days after the pre-exposure. These findings suggest that epinephrine could modulate memory formed in the latent learning.

Comprehensive inelastic neutron scattering study of the multiferroic M n 1 - x C o x W O 4 .

Using high-resolution inelastic neutron scattering, we examine the spin dynamics of M n 1 - x C o x W O 4 in the collinear AF1, the a c - b spiral AF2, and the a c cycloidal AF5 phases. The spin wave excitations are well described by a Heisenberg model with competing long-range exchange interactions ( J i up to 12th nearest neighbors) and the single-ion anisotropy K induced by the spin-orbit interaction. While the exchange constants are relatively unchanged, the dominant effect of doping is to change the single-ion anisotropy from easy axis ( K > 0 ) in the collinear AF1 phase to easy plane ( K < 0 ) in the two multiferroic phases.

The hippocampus integrates context and shock into a configural memory in contextual fear conditioning.

Contextual fear conditioning involves forming a representation for the context and associating it with a shock, which were attributed by the prevailing view to functions of the hippocampus and amygdala, respectively. Yet our recent evidence suggested that both processes require integrity of the dorsal hippocampus (DH). In view of the DH involvement in uniting multiple stimuli into a configuration, this study examined whether the DH would integrate context and shock into a shocked-context representation. Male Wistar rats were trained on a two-phase training paradigm of contextual fear conditioning. They explored a novel context on the first day to acquire a contextual representation, and received a shock in that context on the second day to form the context-shock memory. Tests of conditioned freezing given on the following days revealed two properties of configural memory-direct and mediated pattern completion: First, the contextual fear memory was retrieved in a novel context by a cue embedded in the configural set-a shock that did not elicit significant freezing on its own. Second, freezing was also elicited in a novel context by a transportation chamber that was not directly paired with the shock but could activate the fear memory inferentially. The effects were specific to the cue and not due to context generalization. Infusion of lidocaine into the DH, but not the amygdala, immediately after context-shock training impaired conditioned freezing elicited through either type of pattern completion. Our data suggest that the DH in contextual fear conditioning associates context and shock in parallel with the amygdala by incorporating the shock into an otherwise neutral context representation and turning it into a shocked-context representation. © 2016 Wiley Periodicals, Inc.

Interactions of the dorsal hippocampus, medial prefrontal cortex and nucleus accumbens in formation of fear memory: difference in inhibitory avoidance learning and contextual fear conditioning.

Learning active or reactive responses to fear involves different brain circuitry. This study examined how the nuclus accumbens (NAc), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) may interact in memory processing for these two kinds of responses. Male Wistar rats with cannulae implanted in these areas were trained on a contextual fear conditioning or inhibitory avoidance task that respectively engaged a reactive or active response to fear in the test. Immediately after training, a memory modulating factor released by stress, norepinephrine (NE), was infused into one region and 4% lidocaine into another to examine if an upstream activation effect could be blocked by the downstream suppression. Retention tested 1 day later showed that in both tasks posttraining infusion of NE at different doses into either the DH or mPFC enhanced retention but the enhancement was blocked by concurrent infusion of lidocaine into the other region, suggesting reliance of the effect on functional integrity of both regions. Further, posttraining intra-NAc lidocaine infusion attenuated memory enhancement of NE infused to the DH or mPFC in the inhibitory avoidance task but did not do so in contextual fear conditioning. These results suggest that NE regulation of memory formation for the reactive and active responses to fear may rely on distinct interactions among the DH, mPFC and NAc.

Functional connectivity changes during consolidation of inhibitory avoidance memory in rats: a manganese-enhanced MRI study.

Consolidation of memory involves transfer of encoded information into a durable neural representation, but how this is transacted in the nervous system remains elusive. It has been proposed that memory consolidation is subserved by formation of a cell assembly due to coincidence of pre- and post-synaptic activity therein after learning. To capture such off-line changes, manganese-enhanced magnetic resonance imaging (MEMRI) was used to trace brain activity during the memory consolidation period. Male Wistar rats were trained on the one-trial inhibitory avoidance task and received intraventricular infusion of manganese ion shortly after training. The MEMRI taken 1 day later showed that brain areas including the prelimbic, insular and anterior pirifrom cortices of the learning group had significantly lower memory-related MEMRI signal than those of the control group. The functional network was revealed by correlating the MEMRI signals among regions followed by graph theoretical analysis. Learning sculpted the non-discriminative connectivity among many brain regions in the controls into a network in the trained rats with selected connectivity among regions implicated in inhibitory avoidance learning. The network could be organized into three clusters presumably subserving different functions. The results suggest that the brain prunes excessive functional connectivity in a cell assembly to consolidate new memory.

Roles of hippocampal GABA(A) and muscarinic receptors in consolidation of context memory and context-shock association in contextual fear conditioning: a double dissociation study.

Contextual fear conditioning involves forming a context representation and associating it to a shock, both of which involved the dorsal hippocampus (DH) according to our recent findings. This study tested further whether the two processes may rely on different neurotransmitter systems in the DH. Male Wistar rats with cannula implanted into the DH were subjected to a two-phase training paradigm of contextual fear conditioning to separate context learning from context-shock association in two consecutive days. Immediately after each training phase, different groups of rats received bilateral intra-DH infusion of the GABA(A) agonist muscimol, 5HT(1A) agonist 8-OH-DPAT, NMDA antagonist APV or muscarinic antagonist scopolamine at various doses. On the third day, freezing behavior was tested in the conditioning context. Results showed that intra-DH infusion of muscimol impaired conditioned freezing only if it was given after context learning. In contrast, scopolamine impaired conditioned freezing only if it was given after context-shock training. Posttraining infusion of 8-OH-DPAT or APV had no effect on conditioned freezing when the drug was given at either phase. These results showed double dissociation for the hippocampal GABAergic and cholinergic systems in memory consolidation of contextual fear conditioning: forming context memory required deactivation of the GABA(A) receptors, while forming context-shock memory involved activation of the muscarinic receptors.

Post-training infusion of glutamate into the bed nucleus of the stria terminalis enhanced inhibitory avoidance memory: an effect involving norepinephrine.

This study examined an interaction between glutamate and norepinephrine in the bed nucleus of the stria terminalis (BNST) in modulating affective memory formation. Male Wistar rats with indwelling cannulae in the BNST were trained on a one-trial step-through inhibitory avoidance task and received pre- or post-training intra-BNST infusion of glutamate, norepinephrine or their antagonists. Results of the 1-day test indicated that post-training intra-BNST infusion of DL-2-amino-5-phosphonovaleric acid (APV) impaired retention in a dose- and time-dependent manner, while infusion of glutamate had an opposite effect. Co-infusion of 0.2microg glutamate and 0.02microg norepinephrine resulted in marked retention enhancement by summating non-apparent effects of the two drugs given at a sub-enhancing dose. The amnesic effect of 5.0microg APV was ameliorated by 0.02microg norepinephrine, while the memory enhancing effect of 1.0microg glutamate was attenuated by 5.0microg propranolol. These findings suggest that training on an inhibitory avoidance task may alter glutamate neurotransmission, which by activating NMDA receptors releases norepinephrine to modulate memory formation via beta adrenoceptors in the BNST.

Posttraining infusion of cholinergic drugs into the ventral subiculum modulated memory in an inhibitory avoidance task: interaction with the bed nucleus of the stria terminalis.

The ventral subiculum (vSUB), a hippocampal efferent target implicated in learning and stress coping, receives cholinergic input and sends glutamatergic output to the bed nucleus of the stria terminalis (BNST). This study examined the roles of vSUB muscarinic activation and its interaction with BNST N-methyl-D-aspartate and noradrenergic receptors in formation of aversive memory. Male Wistar rats with cannulae implanted into the vSUB or BNST were trained on a step-through inhibitory avoidance task. Shortly after training, they received cholinergic drugs infused into the vSUB and/or glutamatergic or noradrenergic drugs infused into the BNST. Results of the 1-day retention tests showed that intra-vSUB infusion of oxotremorine (0.01 microg) or scopolamine (0.3 or 3.0 microg) enhanced or impaired retention, respectively. Both effects were dose- and time-dependent, and 0.001 microg oxotremorine attenuated the amnesia induced by 3.0 microg scopolamine. The oxotremorine-induced memory enhancement was blocked by intra-BNST infusion of DL-2-amino-5-phosphonovaleric acid or propranolol at a dose not affecting retention; the amnesia induced by scopolamine was blunted by intra-BNST infusion of glutamate or norepinephrine at a dose with a negligible effect on retention. These data suggest that in an inhibitory avoidance task muscarinic activation of the vSUB modulated memory formation by interacting with the BNST glutamatergic and noradrenergic functions.

Structural and optical studies of high dielectric constant (Na(0.5)A(0.5))Cu(3)Ti(4)O(12) (A = La and Bi).

We report x-ray powder diffraction and temperature-dependent infrared reflectivity measurements of (Na(0.5)La(0.5))Cu(3)Ti(4)O(12) and (Na(0.5)Bi(0.5))Cu(3)Ti(4)O(12) in order to investigate the origin of their lower room-temperature dielectric constants in comparison with the giant value of CaCu(3)Ti(4)O(12). Substituting Ca with Na/La or Na/Bi is found to decrease all Ti-O-Ti angles by the TiO(6) octahedra tilts, resulting in an increase of the local structural disorder on the Na/La and Na/Bi compounds. Further, several infrared-active phonon modes show a broadening in their linewidths, reflecting that the coherency in these vibrational modes is degraded by disorder. Additionally, the lowest-frequency mode of the Ca material is observed to strengthen dramatically at low temperatures, but to a lesser extent in the Na/La and Na/Bi compounds. These results suggest the important role of the local structural disorder on the anomalous low-frequency dielectric response in these materials.

Infusion of lidocaine into the dorsal hippocampus before or after the shock training phase impaired conditioned freezing in a two-phase training task of contextual fear conditioning.

Learning in a contextual fear conditioning task involves forming a context representation and associating it with a shock. The dorsal hippocampus (DH) is implicated in representing the context, but whether it also has a role in associating the context and shock is unclear. To address this issue, male Wistar rats were trained on the task by a two-phase training paradigm, in which rats learned the context representation on day 1 and then reactivated it to associate with the shock on day 2; conditioned freezing was tested on day 3. Lidocaine was infused into the DH at various times in each of the two training sessions. Results showed that intra-DH infusion of lidocaine shortly before or after the context training session on day 1 impaired conditioned freezing, attesting to the DH involvement in context representation. Intra-DH infusion of lidocaine shortly before or after the shock training session on day 2 also impaired conditioned freezing. This deficit was reproduced by infusing lidocaine or APV (alpha-amino-5-phosphonovaleric acid) into the DH after activation of the context memory but before shock administration. The deficit was not due to drug-induced state-dependency, decreased shock sensitivity or reconsolidation failure of the contextual memory. These results suggest that in contextual fear conditioning integrity of the DH is required for memory processing of not only context representation but also context-shock association.

Pre- and post-training infusion of prazosin into the bed nucleus of the stria terminalis impaired acquisition and retention in a Morris water maze task.

The bed nucleus of the stria terminalis (BNST) is interconnected with the amygdala that is implicated in memory modulation. In view of the innervation of this structure by the hippocampus and brain stem noradrenergic nuclei, this study examined the role of BNST noradrenergic activity in acquisition, formation and expression of spatial memory. Male Wistar rats with indwelling cannulae in the BNST were trained on a spatial navigation task in the Morris water maze. Groups of rats received intra-BNST infusion of vehicle, norepinephrine, prazosin or both drugs shortly before or after each daily training session, or shortly before retention tests. Results showed that pre- or posttraining infusion of 1.0 microg prazosin impaired acquisition and retention, but the treatment had no effect on a cued response task. Posttraining infusion of 1.0 microg norepinephrine enhanced acquisition and retention, and this enhancing effect was blocked by simultaneous infusion of 0.3 microg prazosin. Pretest intra-BNST of prazosin or norepinephrine at a dose of 1.0 microg did not impair expression of the spatial navigation memory. These findings suggest that the BNST noradrengergic function is involved in modulating acquisition and formation of spatial memory that engage the hippocampus.

Amphetamine induced sensitization in acoustic startle: lack of blockade by adrenalectomy and alpha-helical CRF9-41.

The present study utilized the acoustic startle response to evaluate the sensitization effect of repeated administration of amphetamine (AMPH). Intraperitoneal injections of AMPH induced a dose-dependent enhancement of startle: 5.0 mg/kg caused a robust effect, 1.0 or 3.0 mg/kg caused a negligible effect. Sensitization was generated by repeated administration of 5.0 mg/kg AMPH for 7 consecutive days and tested on the 8th and 9th days with challenge of saline and 3 mg/kg AMPH. The results showed that rats receiving chronic injections of AMPH, but not saline, showed significant enhancement of startle to 3.0 mg/kg AMPH, and this effect lasted at least for a month. To explore the role of the hypothalamo-pituitary-adrenal axis in this sensitization effect, rats received adrenalectomy, adrenal demedullation, or sham adrenal operation, and then were subjected to acute or chronic injections of 5.0 mg/kg AMPH. Removal of the whole adrenal gland or only the medulla abolished neither the startle enhancing effect of AMPH injected acutely nor the sensitization effect of AMPH injected chronically. In addition, intracerebroventricular infusion of a CRF antagonist, alpha-helical CRF9-41, prior to the challenge test failed to alter the sensitization effect of AMPH. These findings suggest that neither adrenal hormones nor CRF was indispensable for induction/expression of AMPH-induced sensitization in acoustic startle.

Posttraining infusion of norepinephrine and corticotropin releasing factor into the bed nucleus of the stria terminalis enhanced retention in an inhibitory avoidance task.

The present study investigated whether the bed nucleus of the stria terminalis (BNST) is involved in formation and retrieval of affective memory. Male Wistar rats with cannulae bilaterally implanted into the BNST were trained on a one-trial step-through inhibitory avoidance task. Shortly after training they received bilateral intra-BNST infusion of lidocaine, various noradrenergic drugs, or corticotropin releasing factor (CRF). Results showed that posttraining intra-BNST infusion of lidocaine impaired retention. Posttraining intra-BNST infusion of norepinephrine or the alpha1 antagonist prazosin induced a dose- and time-dependent retention enhancement or deficit, respectively. The enhancing effect of norepinephrine was mimicked by the alpha1 agonist phenylephrine, and antagonized by prazosin at a non-impairing dose. Posttraining intra-BNST infusion of the alpha2 antagonist idazoxan or the beta antagonist propranolol failed to affect retention. Posttraining intra-BNST infusion of CRF also enhanced retention in a dose-dependent manner. Various drugs infused shortly before testing did not significantly influence locomotor activity and retention. These findings, taken together, suggest that the BNST is involved in memory formation processes for affective experience and norepinephrine released in the BNST acting via alpha1 receptors plays a critical role in this function.

Startle responses to electric shocks: measurement of shock sensitivity and effects of morphine, buspirone and brain lesions.

The present study developed a new protocol to assess shock sensitivity in rats. Male Wistar rats were subjected to footshock stimuli ranging from 0 to 1.6 mA (0.1 s) in a startle apparatus and startle responses elicited by shocks were measured. Acoustic stimuli (95, 105, or 115 dB) were dispersed within the shock series serving as a control measurement of motor performance. Results indicated that the magnitude of shock startle responses significantly increased with the shock intensity in a linear trend. Morphine (8.0 mg/kg) and buspirone (1.0, 2.5, or 5.0 mg/kg), both of which possessing analgesic effects, depressed shock startle but had no such effect on acoustic startle. The effect of morphine was readily reversed by pretreatment of naloxone (1.0 mg/kg). To investigate the neural basis underlying this response, radio-frequency lesions of various structures implicated in processing of nociceptive or aversive information were undertaken. Lesions of the ventroposterior thalamic nucleus, insular cortex, or amygdala decreased startle reactivity to electric shocks but not to acoustic stimuli. Lesions of the anterior cingulate gyrus or medial prefrontal cortex, while altered the reactivity to acoustic stimuli, had no effect on the shock-elicited startle. These results suggested that the amplitude of startle in response to electric shocks provide a quantitative measurement of shock sensitivity within an extended range of stimulus intensities. Performing this response may engage the the central nociceptive pathway.

Pre- or post-training injection of buspirone impaired retention in the inhibitory avoidance task: involvement of amygdala 5-HT1A receptors.

The present study investigated the effect of buspirone on memory formation in an aversive learning task. Male Wistar rats were trained on the inhibitory avoidance task and tested for retention 1 day after training. They received peripheral or intra-amygdala administration of buspirone or other 5-HT1A drugs either before or after training. Results indicated that pretraining systemic injections of buspirone caused a dose-dependent retention deficit; 5. 0 mg/kg had a marked effect and 1.0 mg/kg had no effect. Post-training injections of the drug caused a time-dependent retention deficit, which was not due to a state-dependent effect on retrieval. When training in the inhibitory avoidance task was divided into a context-training phase and a shock-training phase, buspirone impaired retention only when administered in the shock-training phase, suggesting that the drug influenced memory processing of affective events. Further results indicated that post-training intra-amygdala infusion of buspirone or the 5-HT1A agonist 8-hydroxy-di-n-propylaminotetralin (8-OH-DPAT) caused a time-dependent and dose-dependent retention deficit. Post-training intra-amygdala infusion of the 5-HT1A antagonist WAY100635 (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)-N-(2-pyridyl) cyclohexane carboxamine maleate) attenuated the memory-impairing effects of buspirone. These findings suggest that buspirone may modulate memory storage processes in the inhibitory avoidance task through an action on amygdaloid 5-HT1A receptors.

WaveGuide: a joint wavelet-based image representation and description system.

Data representation and content description are two basic components required by the management of any image database. A wavelet based system, called the WaveGuide, which integrates these two components in a unified framework, is proposed in this work. In the WaveGuide system, images are compressed with the state-of-the-art wavelet coding technique and indexed with color, texture, and object shape descriptors generated in the wavelet domain during the encoding process. All the content descriptors are extracted by machines automatically with a low computational complexity and stored with a low memory space. Extensive experiments are performed to demonstrate the performance of the new approach.

Buspirone impaired acquisition and retention in avoidance tasks: involvement of the hippocampus.

This study investigated the effects of buspirone on acquisition as well as formation and expression of memory in three different types of avoidance tasks. Rats were trained and tested on a one-trial inhibitory avoidance task, an 8-trial active avoidance task or the Morris water maze. Buspirone (5.0 mg/kg) was administered subcutaneously 30 min before training, immediately after training or 30 min before testing. Retention was tested at various times after training. In the inhibitory avoidance task, pretraining injections of buspirone produced a marked impairing effect on retention, posttraining injections of buspirone produced a moderate but time-dependent memory deficit. Pretest injections of buspirone suppressed retention performance. Such an effect was more pronounced in the 1-day test than in the 21-day test. Intra-hippocampal infusion of buspirone (5.0 micrograms) before testing suppressed expression of the 1-day, but not the 21-day, memory. In the active avoidance task and the Morris water maze, an injection of buspirone before training or testing also impaired acquisition or suppressed retention performance. These findings suggest that buspirone given at various times could compromise acquisition, consolidation and retrieval of affective memory and the hippocampus was involved in the retrieval effect.

Pretraining infusion of DSP-4 into the amygdala impaired retention in the inhibitory avoidance task: involvement of norepinephrine but not serotonin in memory facilitation.

The present study investigated the involvement of amygdala noradrenergic (NE) and serotonergic (5-HT) systems in memory storage processing. Rats bearing chronic cannulae in the amygdala were trained on a one-trial inhibitory avoidance task and tested for retention 24 hrs later. Five days prior to training, rats received intra-amygdala infusion of vehicle or various doses of N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4)-a NE-specific neurotoxin when given peripherally. Results showed that pretraining intra-amygdala infusion of 10.0 micrograms or 30.0 micrograms of DSP-4 impaired retention. Further, 30.0 micrograms of DSP-4 also abolished the memory enhancing effect of epinephrine (E) injected peripherally. However, local infusion of DSP-4 depleted not only NE but also 5-HT and DA substantially. Subsequent experiments found that the retention deficit induced by 30.0 micrograms of DSP-4 could be ameliorated by 0.2 microgram NE but not by 5-HT at a wide range of doses infused into the amygdala shortly after training, which ascribed the deficit to depletion of NE. After protecting the 5-HT terminals by a pretreatment of fluoxetine (15.0 mg/kg), pretraining intra-amygdala infusion of 30.0 micrograms DSP-4 shifted the memory-enhancing dose of E from 0.1 mg/kg to 1.0 mg/kg. In contrast, pretraining intra-amygdala infusion of 15.0 micrograms 5,7-dihydroxytryptamine (5,7-DHT) or DSP-4 with a pretreatment of desipramine (DMI, 25.0 mg/kgx2) to protect NE terminals failed to impair retention or attenuate the memory enhancing effect of 0.1 mg/kg E injected peripherally. These findings, taken together, suggest that the memory modulatory effect of peripheral E involved, at least partially, the amygdala NE system.

Inhibitory avoidance learning alters the amygdala calcium/calmodulin-dependent protein kinase II activity in rats.

This study investigated the role of amygdala CaM-kinase II (calcium/calmodulin-dependent protein kinase II) in affective learning and memory. In Experiment I, two groups of rats were trained on a one-trial step through inhibitory avoidance learning task. The experimental group received a high intensity foot shock contingent upon the stepping-through behavior, whereas the control group received a series of non-contingent low intensity foot shock during training. The experimental rats showed significantly higher retention scores than the control rats. Correspondingly, rats in the experimental group showed significantly higher Ca2+-independent activity of CaM-kinase II than the controls. Intra-amygdala injection of a specific CaM-kinase II inhibitor, KN-62, before the training trial disrupted affective learning. In comparison with the vehicle-injected controls, pretraining injection of KN-62 impaired the acquisition of affective specific learning. These results, taken together, indicated that the activation of amygdala CaM-kinase II in the amygdala is associated with the affective learning behavior, and may be one of the neural mechanisms underlying formation of affective memory.

Spatial learning alters hippocampal calcium/calmodulin-dependent protein kinase II activity in rats.

This study investigated the role of hippocampal CaM-kinase II (calcium/calmodulin-dependent protein kinase II) in spatial learning. In Experiment I, three groups of rats received 1, 2 or 5 days of training on a spatial task in the Morris water maze with a hidden platform, while a control group was trained on a nonspatial task with a visible platform. The acquisition rate in the spatial task was slower than that in the nonspatial task. However, rats receiving 5 days of spatial training had the highest Ca(2+)-independent activity of CaM-kinase II compared with the controls receiving nonspatial training and rats having 1 or 2 days of spatial training. Furthermore, the level of hippocampal Ca2+-independent CaM-kinase II activity was correlated with the final performance on the spatial task. In Experiment II, rats received intra-hippocampal injections of a specific CaM-kinase II inhibitor-KN-62-before each training session. In comparison with the vehicle-injected controls, pretraining injection of KN-62 retarded acquisition in the spatial task but had no effect on the nonspatial task. These results, taken together, indicated that the activation of CaM-kinase II in the hippocampus is not only correlated to the degree of spatial training on the Morris water maze, but may also underlie the neural mechanism subserving spatial memory.