Modulation Of Memory Storage Research Articles

Amygdala regulation of immediate-early gene expression in the hippocampus induced by contextual fear conditioning.

The basolateral nuclei of the amygdala (BLA) are thought to modulate memory storage in other brain regions (McGaugh, 2004). We reported that BLA modulates the memory for both an explored context and for contextual fear conditioning. Both of these memories depend on the hippocampus. Here, we examined the hypothesis that the BLA exerts its modulatory effect by regulating the expression of immediate-early genes (IEGs) in the hippocampus. The main findings of these experiments were: (1) Arc activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) and c-fos mRNA are induced in the hippocampus after a context exposure, or context plus shock experience, but not after an immediate shock; and (2) BLA inactivation with muscimol attenuated the increase in Arc and c-fos mRNA in the hippocampus associated with contextual fear conditioning but did not influence Arc mRNA associated with context exploration. These results support the hypothesis that the amygdala modulates contextual fear memory by regulating expression of IEGs in the hippocampus.

Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus

Activation of beta-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the beta-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance.

Amygdala modulation of parahippocampal and frontal regions during emotionally influenced memory storage

Considerable evidence from both animal and human subject research supports the hypothesis that the amygdala, when activated by emotional arousal, modulates memory storage processes in other brain regions. By this hypothesis, changes in the functional interactions of the amygdala with other brain regions during emotional conditions should underlie, at least in part, enhanced memory for emotional material. Here we examined the influence of the human amygdala on other brain regions under emotional and nonemotional learning conditions using structural equation modeling (SEqM). Eleven male subjects received two PET scans for regional cerebral glucose metabolism—one scan while viewing a series of emotionally provocative (negative) film clips and a second scan while viewing a series of more emotionally neutral film clips. Enhanced activity in the right amygdala was related to enhanced memory for the emotional films. To identify potential candidate voxels for SEqM, the functional connectivity of the maximally activated voxel within the right amygdala was investigated using partial least squares. A subset of regions identified by this analysis showing differences functional connectivity with the amygdala between the emotional versus neutral film conditions were then submitted to SEqM, which revealed significantly increased amygdala influences on the ipsilateral parahippocampal gyrus and ventrolateral prefrontal cortex during the emotional relative to the neutral film viewing condition. These findings support the view that increased influences from the amygdala, presumably reflecting its memory-modulation function, occur during emotionally arousing learning situations.

Enhancement of noradrenergic neurotransmission in the nucleus of the solitary tract modulates memory storage processes

These studies examined whether posttraining activation of α1-noradrenergic receptors in the nucleus tractus solitarius (NTS) influences neural processes that are involved in encoding information into memory. Different groups of male Sprague–Dawley rats were trained in two separate learning tasks. In experiment 1, rats were given either a control solution or the α1-noradrenergic agonist phenylephrine (0.5, 1.0, 5.0, or 10 μg/0.5 μl) directly into the NTS immediately after they were given a footshock (0.35 mA, 0.5 s) in the dark compartment of an inhibitory apparatus. In a retention test given 48 h later, groups that received either 5.0 or 10.0 μg of phenylephrine avoided the dark compartment for a significantly longer period of time than the PBS control group ( P<0.05 and P<0.01, respectively). In experiment 2, identical doses of phenylephrine were infused in the NTS following footshock delivery in one alley of a Y-maze. Animals given either 1.0 or 5.0 μg of phenylephrine performed significantly better than PBS controls on several different measures that served as indices of retention. The results indicate that activation of α1-noradrenergic receptors in the NTS plays a critical role in the transmission of signals from the periphery to brain systems that process memory for emotionally significant experiences.

Modulation of memory consolidation for olfactory learning by reversible inactivation of the basolateral amygdala.

The role of the basolateral amygdala (BLA) in the consolidation of an association between an olfactory stimulus and footshock was investigated with a reversible lesion technique of post-training intra-BLA infusions of tetrodotoxin. Rats receiving tetrodotoxin infusions following paired odor-shock presentations spent more time near the odor, and reacted differently on contact with the odor when tested 24 hr after training, than did rats receiving paired presentations and saline infusions, but they did not differ from rats receiving unpaired presentations and saline infusions. The results indicate that the BLA plays a similar role in influencing consolidation of olfactory-based memory as it does for memory based on other modalities. Thus, these findings strengthen the view that the BLA plays a general role in modulation of memory storage for emotionally arousing events.

Light and electron microscopic study of cholinergic and noradrenergic elements in the basolateral nucleus of the rat amygdala: evidence for interactions between the two systems.

Pharmacological studies have suggested that the cholinergic (ACh) and noradrenergic (NA) systems in the amygdala (AM) play an important role in learning and memory storage and that the two systems interact to modulate memory storage. To obtain anatomical evidence for the interaction, the organization of the ACh and NA fibers in rat AM was investigated by immunocytochemistry for choline acetyltransferase (ChAT) and dopamine-beta-hydroxylase (DBH) in conjunction with light, confocal laser scanning, and electron microscopy (LM, CLSM, and TEM, respectively). LM showed that the ChAT immunoreactivity was densest in the basolateral nucleus (BL), whereas the DBH immunoreactivity was densest in the posterior BL. CLSM demonstrated that the ChAT-immunoreactive profiles in the BL were frequently located in juxtaposition to the DBH-immunoreactive axons. The TEM observations were as follows: The majority of the synapses formed by ChAT-immunoreactive terminals were symmetric, but DBH-immunoreactive axons formed both asymmetric and symmetric synapses. The ChAT-immunoreactive terminals usually established the symmetric synaptic contacts with the DBH-immunoreactive terminals and varicosities. The DBH-immunoreactive terminals formed the asymmetric synapses with the ChAT-immunoreactive dendrites of the intrinsic neurons within the AM. The results provide anatomical substrates for mnemonic functions of the ACh and NA systems and for the interactions between the two systems in the AM.

The effects of noradrenergic activation of the nucleus tractus solitarius on memory and in potentiating norepinephrine release in the amygdala.

Although it is known that norepinephrine (NE) modulates memory by acting on limbic areas, few studies describe how structures supplying NE to the limbic system, such as the nucleus tractus solitarius (NTS) contribute to this process. The present study examined the effects on memory of activating the NE pathway between the NTS and the amygdala (AMYG). Rats received buffer or the beta-noradrenergic agonist clenbuterol (CLN; 10, 50, or 100 ng/0.5 microl) into the NTS after footshock training in a Y-maze discrimination task. Infusion of 100 ng CLN significantly improved memory when retention was tested in the absence or presence of cues associated with the footshock. Experiment 2 used in vivo microdialysis to determine whether the mnemonic effects of CLN are mediated by influencing NE output in the AMYG. Subjects were given an intra-NTS infusion of CLN or phosphate buffered saline, footshock (0.8 mA, 1 s), and injected with epinephrine (EPI; 0.3 mg/kg ip) or saline. CLN or EPI injection produced a significant increase in NE sampled from the AMYG. These findings indicate that activation of NTS neurons that project to and release NE in the AMYG modulates memory storage processing.

Memory Improvement by Post-trial Injection of Lidocaine into the Tuberomammillary Nucleus, the Source of Neuronal Histamine

Brain histamine is exclusively contained within and released from neurons whose cell bodies are clustered in the tuberomammillary nucleus (TM) of the posterior hypothalamus. This experiment examined the effects of a transient inactivation of the TM on inhibitory avoidance learning. Rats with chronically implanted cannulae were tested on a 1-trial step-through avoidance task. Immediately following training, the rats received unilateral intra-TM infusions (0.5 μl) of lidocaine (5 or 20 μg). Control groups included vehicle-injected rats and a group given an injection of 20 μg lidocaine 5 h after training. When tested 24 h later, rats treated with 20 μg lidocaine exhibited longer step-through latencies than vehicle-treated controls, indicative of superior learning of the task. The failure of the delayed post-trial injection of lidocaine to significantly influence step-through latencies indicates that the compound influenced learning by modulating memory storage processes rather than by acting on performance variables during retrieval of the task. Thus, inactivation of the TM by lidocaine can exert facilitatory effects on mnemonic processing, which might be related to a temporary reduction of histaminergic activity during the early phase of memory consolidation.

Basolateral Amygdala Noradrenergic Influences on Memory Storage Are Mediated by an Interaction between β- and α1-Adrenoceptors

Extensive evidence indicates that norepinephrine modulates memory storage through an activation of beta-adrenoceptors in the basolateral nucleus of the amygdala (BLA). Recent findings suggest that the effects of beta-adrenergic activation on memory storage are influenced by alpha1-adrenoceptor stimulation. Pharmacological findings indicate that activation of postsynaptic alpha1-adrenoceptors potentiates beta-adrenoceptor-mediated activation of cAMP formation. The present study examined whether inactivation of alpha1-adrenoceptors in the BLA would alter the dose-response effects on memory storage of intra-BLA infusions of a beta-adrenoceptor agonist, as well as that of a synthetic cAMP analog. Male Sprague Dawley rats received bilateral microinfusions into the BLA of either the beta-adrenoceptor agonist clenbuterol (3-3000 pmol in 0.2 microliter) or 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo-cAMP) (0.2-7 nmol in 0.2 microliter) alone or together with the alpha1-adrenoceptor antagonist prazosin (0.2 nmol) immediately after training in an inhibitory avoidance task. Retention was tested 48 hr later. Clenbuterol induced a dose-dependent enhancement of retention, and prazosin attenuated the dose-response effects of clenbuterol. Posttraining intra-BLA infusions of 8-bromo-cAMP also induced a dose-dependent enhancement of retention latencies. However, concurrent infusion of prazosin did not alter the dose-response effects of 8-bromo-cAMP. These findings are consistent with the view that alpha1-adrenoceptors affect memory storage by modulating beta-adrenoceptor activation in the BLA. Moreover, these findings are consistent with those of pharmacological studies indicating that beta-adrenoceptors modulate memory storage by a direct coupling to adenylate cyclase, whereas alpha1-receptors act indirectly by influencing the beta-adrenoceptor-mediated influence on cAMP formation.

Involvement of α 1-adrenoceptors in the basolateral amygdala in modulation of memory storage

These experiments examined the involvement of α 1-adrenoceptors in the basolateral amygdala and their interaction with β-adrenoceptors in modulating memory storage. In Experiment 1, male Sprague–Dawley rats, implanted with bilateral cannulae in the basolateral amygdala, were trained in a one-trial inhibitory avoidance task and immediately after training, were given microinfusions (0.2 μl/side) of the selective α 1-adrenoceptor antagonist, prazosin (0.1–1.0 μg). Retention was tested 48 h later. Prazosin induced a dose-dependent impairment in retention performance. In Experiment 2, animals received post-training intra-basolateral amygdala infusions of phenylephrine (a non-selective α-adrenoceptor agonist; 1.0–10.0 μg) alone or in combination with yohimbine (a selective α 2-adrenoceptor antagonist; 0.2 μg) to examine the effects, on memory storage, of selective α 1-adrenoceptor activation. Low doses of phenylephrine alone tended to impair retention performance, whereas the highest dose was non-effective. In contrast, phenylephrine infused together with yohimbine induced a dose-dependent enhancement of retention performance, suggesting that a selective activation of α 1-adrenoceptors enhances memory formation. In Experiment 3, animals received intra-basolateral amygdala infusions of phenylephrine (1.0–10.0 μg) and yohimbine (0.2 μg) in combination with atenolol (a β 1-adrenoceptor antagonist; 1.0 μg). Atenolol blocked the memory-enhancing effects induced by infusions of phenylephrine together with yohimbine. Considered together, these findings suggest that α 1-adrenoceptors in the basolateral amygdala are implicated in mediating the effects of norepinephrine on memory storage and that their action depends on concurrent β-adrenoceptor activation.

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.

Glucocorticoid receptor activation in the rat nucleus of the solitary tract facilitates memory consolidation: involvement of the basolateral amygdala.

These experiments examined the involvement of glucocorticoid receptors (GRs or type II) located in the A2-noradrenergic cell group of the rat nucleus of the solitary tract (NTS) in modulating memory storage. Bilateral intra-NTS infusions (0.5 microL) of the specific GR agonist RU 28362 (11beta, 17beta-dihydroxy-6, 21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one), in doses ranging from 0.01 to 10.0 ng, immediately after inhibitory avoidance training produced a dose-dependent enhancement of 48 h retention performance. Infusions of 0.1 or 1.0 ng of the agonist enhanced retention, whereas lower or higher doses were ineffective. Post-training infusions of the GR antagonist RU 38486 [17beta-hydroxy-11beta-(4-dimethylaminophenyl)-17alpha-(1-pr opynyl)-o estra-4,9-dien-3-one, 0.01-10.0 ng] into the NTS did not significantly affect retention performance, but shifted the dose-response effects of post-training systemic injections of the synthetic glucocorticoid dexamethasone to the right. These results indicate that activation of GRs in the NTS can influence memory formation for inhibitory avoidance training, and suggest that the effects of circulating glucocorticoids on memory are mediated, in part, by an activation of GRs in the NTS. Additionally, pretraining infusions of the beta1-adrenergic antagonist atenolol (0.5 microg in 0.2 microL) into the basolateral nucleus of the amygdala (BLA), a brain structure which receives noradrenergic projections from the NTS and is implicated in memory storage modulation, blocked the memory-enhancing effects of the GR agonist (1.0 ng) infused into the NTS. These findings provide evidence that memory storage is modulated by glucocorticoid binding to GRs in noradrenergic cell bodies in the NTS and suggest that these modulatory effects are conveyed by ascending projections to the BLA.

Norepinephrine Infused into the Basolateral Amygdala Posttraining Enhances Retention in a Spatial Water Maze Task

Recent evidence indicates that the amygdala plays a role in modulating memory processes in other brain regions. For example, posttraining intra-amygdala infusions of amphetamine enhanced memory in both spatial and cued training water maze tasks; these tasks are known to depend on the integrity of the hippocampus and caudate nucleus, respectively. To determine whether this modulation is dependent on noradrenergic activation within a subregion of the amygdala (the basolateral nucleus), the present study examined the effects of posttraining microinfusions (0.2 μl) of norepinephrine or propranolol into the basolateral amygdala immediately following training in a spatial version of the water maze task. Rats received a four-trial training session on each of 2 consecutive days. On the third day, rats were given a 60-s probe test in the absence of a platform. Retention latencies obtained on the second training day revealed that norepinephrine dose-dependently enhanced retention for the location of the hidden platform. In contrast, propranolol significantly impaired retention. Probe trial analysis revealed that rats treated with 0.25 μg norepinephrine demonstrated a selective spatial bias for the training platform location relative to all other groups. These findings are consistent with others and support the view that the basolateral amygdala has a role in modulating memory storage by interacting with other brain regions.

Effects of GABA B receptor antagonism on the development of Pentylenetetrazol-induced kindling in mice

Pentylenetetrazol (PTZ) administered chronically in rodents induces kindling which is considered to be a model of chronic epilepsy mediated through a specific interaction with the GABA-gated chloride ionophore. PTZ kindling also impairs shuttle-box learning indicating a possible modulation of memory storage [A. Becker, G. Grecksch, H. Mathies. The influence of diazepam on learning processes impaired by pentylenetetrazol kindling. Naunyn-Schmiedeberg's Arch. Pharmacol. 349 (1994) 429-496]. Since GABA B receptor antagonism has been shown to improve cognitive performance in rodents and primates we have examined the effects of 3 antagonists: CGP 36742 (3-amino-propyl- n-butyl-phosphinic acid), CGP 56433 ([3-{1-( S)-[{3-(cyclohexylmethyl) hydroxyphosphinyl]-2-( S)-hydroxypropyl]-amino]ethyl]benzoic acid) and CGP 61334 ([3-{[3[(diethoxymethyl)hydroxyphosphinyl]-propyl]-amino}methyl]-benzoic acid) on the induction of PTZ kindling in mice at 48 h intervals for 8 weeks. Subsequently the mice were tested in an active avoidance paradigm. At the end of the experiment GABA B receptor autoradiography was performed on brain sections from these animals. Seizure intensity increased progressively in control mice reaching by 8 weeks a mean score which corresponded to clonic seizures. The GABA B antagonists suppressed kindling during the first 4 weeks and after that restored the seizure intensity to the level of control animals. The level of kindling was proportional to the avoidance score. The density of GABA B receptor binding in brain sections from PTZ kindled mice was significantly greater than in controls. This was not altered by pretreatment with the GABA B antagonists except in the cerebellum.

Posttraining Electrical Stimulation of Vagal Afferents with Concomitant Vagal Efferent Inactivation Enhances Memory Storage Processes in the Rat

Peripherally administered or released substances that modulate memory storage, but do not freely enter the brain, may produce their effects on memory by activating peripheral receptors that send messages centrally through the vagus nerve. Indeed, vagus nerve stimulation enhances memory performance, although it is unclear whether this effect is due to the activation of vagal afferents or efferents. To eliminate the possible influence of descending fibers on memory storage processes, rats were implanted with cuff electrode/catheter systems along the left cervical vagus. Forty-eight hours following surgery, each animal received a 3.0-μl infusion (1.0 μl/min) of either lidocaine hydrochloride (75.0 mM) or isotonic saline below the point of stimulation. Animals were then trained 10 min later on an inhibitory-avoidance task with a 0.75-mA, 1.0-s foot shock. Sham stimulation or vagus nerve stimulation (0.5-ms biphasic pulses; 20.0 Hz; 30 s; 0.2, 0.4, or 0.8 mA) was administered immediately after training. Memory, tested 24 h later, was enhanced by stimulation whether descending vagus nerve fibers were inactivated or not. Both lidocaine- and saline-infused groups showed an intensity-dependent, inverted-U-shaped pattern of retention performance, with the greatest effect observed for 0.4 mA (U= 9,p< .05, andU= 7,p< .01, respectively). Additionally, animals that received lidocaine infusions, but no vagus nerve stimulation, showed impaired memory compared to the performance of saline-infused control animals (U= 11,p< .05). Together, these findings suggest that vagal afferents carry messages about peripheral states that lead to the modulation of memory storage and that the memory-enhancing effect produced by vagus nerve stimulation is not mediated via the activation of vagal efferents.

Stress-activated hormonal systems and the regulation of memory storage.

There is little doubt that all experiences are not equally well remembered. Most of our experiences are uneventful events that are generally quickly forgotten or, at best, poorly remembered. Extensive evidence indicates that experiences that are emotionally arousing tend to be well remembered. The strength of memories of events reflects the significance of the event. Although it might be argued that enhanced remembrance of emotionally arousing events results simply from increased attention to these situations or from subsequent thinking about or rehearsing the experiences, considerable evidence supports the hypothesis that emotional responses influence memory, at least in part, by modulating long-term memory storage. Research in our laboratory has focused on the hormonal and brain systems that mediate the effects of emotional arousal on memory storage. This chapter reviews the findings of our experiments using laboratory animals to investigate the effects of stress-released hormones on memory storage. Our findings suggest that stress hormones influence memory storage by activating the amygdala, a brain system known to be involved in emotionally based memory (Davis, this volume; LeDoux, this volume). Furthermore, our findings suggest that the amygdala modulates memory storage in other brain regions. The findings have implications for understanding the role of emotional arousal, stress hormones, and brain systems in normal-human memory as well as pathological memory in patients with posttraumatic stress disorder (YTSD) (Cahill, this volume).'

Glucocorticoid Receptor Agonist and Antagonist Administration into the Basolateral but Not Central Amygdala Modulates Memory Storage

The present study examined the effects, in male Sprague–Dawley rats, of microinfusion of drugs affecting glucocorticoid receptors (GRs or Type II) administered into either the basolateral (BLA) or central nucleus of the amygdala (CEA) on memory for training in an inhibitory avoidance and water-maze escape task. The specific GR agonist RU 28362 (1.0 or 3.0 ng) infused into the BLA immediately after training in a one-trial inhibitory avoidance task dose-dependently enhanced 48-h retention, whereas infusion of the GR agonist into the CEA did not affect retention. Additionally, pretraining microinfusions of the specific GR antagonist RU 38486 (0.3, 1.0, or 3.0 ng) into the BLA, but not infusions into the CEA, impaired memory for escape training to find a submerged platform in a water maze. These findings indicate that glucocorticoids affect memory storage, at least in part, by binding directly to GRs in the BLA and provide further evidence for the view that the BLA is an important brain region in integrating hormonal and neurotransmitter influences on memory storage.

Interaction of neuromodulatory systems in modulating memory storage

An implicit assumption guiding many studies of neurochemical systems involved in learning and memory in animal subjects is that animal and human memory systems use the same or similar mechanisms. Because acquisition and retention performance can be influenced by many processes other than information storage, special effort is required to distinguish influences on memory processes from other factors influencing performance. This article reviews the findings of recent studies investigating the effects, on memory, of drugs affecting adrenergic, opioid peptidergic, GABAergic and cholinergic systems. The review focuses primarily on studies using posttraining treatments and tests for retention given no sooner than a day after the training. Extensive evidence suggests that such drugs interact within the amygdaloid complex and that projections from the amygdala influence memory storage in other brain regions. The assumption that comparable processes occur in animal and human subjects is supported by evidence that, in human subjects, emotionally influenced memory is blocked by a β-adrenergic blocker and by lesions of the amygdaloid complex.

Effects of Posttraining Administration of Glucose on Retention of a Habituation Response in Mice: Participation of a Central Cholinergic Mechanism

Male Swiss mice were allowed to explore a novel environment, provided by an open-field activity chamber, for 10 min. The procedure was repeated twice with a 24-h interval. The difference in the exploratory activity between the first (training) and the second (testing) exposures to the chamber was taken as an index of retention of this habituation task. Posttraining intraperitoneal administration of glucose (10–300 mg/kg) enhanced retention in a dose-related manner, although only the dose of 30 mg/kg of glucose produced significant effects. Thus, the dose–response curve adopted an inverted U-shaped form. Glucose (30 mg/kg) given to untrained mice did not modify their exploratory performance when recorded 24 h later. The effects of glucose on retention were time-dependent, suggesting an action on memory storage. The memory-improving actions of glucose were prevented by the simultaneous administration of both the central acting muscarinic cholinergic antagonist atropine (0.5 mg/kg) and by the central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg). In contrast, neither methylatropine (0.5 mg/kg), a peripherally acting muscarinic receptor blocker, nor hexamethonium (5 mg/kg), a peripherally acting nicotinic receptor blocker, prevented the effects of glucose on retention. Low subeffective doses of glucose (10 mg/kg) and the central anticholinesterase physostigmine (35 μg/kg), but not neostigmine (35 μg/kg), given together, act synergistically and facilitated retention. We suggest that glucose modulates memory storage of one form of learning elicited by stimuli repeatedly presented without reinforcement, probably through an enhancement of brain acetylcholine synthesis and/or its release.

Modulation of memory storage

For several decades, the concept of modulation of memory storage has significantly influenced research investigating neurobiological memory mechanisms. New evidence provides additional support for the view that stress hormones released during emotionally arousing situations modulate memory processes. Recent experiments have investigated the role of sympathetic adrenomedullary hormones in emotional memory in humans, as well as the role of adrenocortical hormones, primarily in animal studies. Further, it is becoming increasingly clear that the sympathetic adrenomedullary and the pituitary adrenocortical systems interact to modulate memory storage. Other new evidence emphasizes the role of peripheral influences to the brain on emotional memory, as well as the critical contribution of the amygdaloid complex in modulation of memory by emotional arousal.