Differential effects of a reminder cue on amnesia induced by stimulation of amygdala and hippocampus.

Examined the effects of a footshock reminder (FSR) in restoring memory after discrete electrical brain stimulation in 119 male Long-Evans rats. Ss received low-level bilateral electrical stimulation of either the amygdala or the hippocampus after training in a 1-trial passive avoidance task. Ss receiving stimulation showed amnesia when tested 24 hrs after training. One hour after the retention test, Ss received an FSR. 23 hrs later in a 2nd retention test, hippocampus-stimulated Ss showed recovery of memory, while amygdala-stimulated Ss did not. Stimulated Ss that did not receive an FSR remained amnesic. In addition, the effects of amygdala and hippocampal stimulation applied after the FSR were examined. On the 2nd retention test, amygdala stimulation disrupted the FSR effect, while hippocampal stimulation had no deleterious effects. Data are interpreted from a memory-attribute point of view that suggests that the amygdala and hippocampus may be differentially involved in the processing of particular attributes of the learning task. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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-microliter infusion (1.0 microliter/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, and U = 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.     

Memory enhancement with posttraining intraventricular glucose injections in rats.

Recent findings suggest that peripheral epinephrine enhancement of memory storage may be mediated in part by an increase in circulating glucose levels subsequent to epinephrine release or injection. Because glucose, unlike epinephrine, has ready access to the central nervous system (CNS), it is possible that glucose acts directly on central processes to enhance memory. To test this possibility, rats were trained on a one-trial inhibitory avoidance task and received immediate or delayed injections of glucose in artificial cerebrospinal fluid. On retention tests 24 hr after training, animals that received 3 or 5 μg glucose (in 1 μl cerebrospinal fluid over 3 min) had significantly enhanced performance of the learned response. Findings are consistent with the view that glucose can regulate the storage of new information by acting on central processes. Whether there are additional peripheral contributions to glucose effects on memory remains to be determined. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraining estrogen and memory modulation

The present paper provides a review of recent research carried out in this laboratory investigating the effects of posttraining peripheral and intrahippocampal injection of estradiol on memory in rats, and estradiol-acetylcholine interactions in memory modulation. Ovariectomized rats received an eight-trial training session in a hippocampal-dependent hidden platform water maze task. Immediately following training, rats received a posttraining peripheral or intrahippocampal injection of estradiol-cyclodextrin complex or vehicle. Twenty-four hours later rats were returned to the maze for a retention test session, and latency to escape was used as a measure of memory for the previous day's training. Peripheral posttraining injection of estradiol enhances memory relative to vehicle-treated rats. Injections of estradiol given 2 h posttraining has no effect on retention, indicating a time-dependent effect of estradiol on memory storage processes. A time-dependent memory enhancing effect of posttraining intrahippocampal injections of estradiol has also been observed in both male and ovariectomized female rats. The memory enhancing effect of peripheral posttraining injection of estradiol in ovariectomized rats is blocked by a subeffective dose of the acetylcholine muscarinic receptor antagonist scopolamine, suggesting that estradiol interacts with cholinergic systems in memory modulation. Concurrent peripheral posttraining injection of a subeffective dose of estradiol and a subeffective dose of the cholinergic agonist oxotremorine produces a synergistic memory enhancing effect. The findings suggest that: (1) estradiol selectively influences memory storage independent of an effect on nonmnemonic processes, (2) the hippocampus is a potential neuroanatomical site of action mediating estrogenic effects on memory, and (3) estradiol interacts with cholinergic systems in memory modulation.     

Glutamatergic transmission in the nucleus of the solitary tract modulates memory through influences on amygdala noradrenergic systems.

The authors examined whether glutamate release from the vagus nerve onto the nucleus of the solitary tract (NTS) is one mechanism by which the vagus influences memory and neural activity in limbic structures. Rats trained to drink from a spout were given a footshock (0.35 mA) on Day 5 after approaching the spout. Phosphate-buffered saline or 5.0, 50.0, or 100.0 nmol/0.5 μl glutamate was then infused into the NTS. Glutamate (5.0 or 50.0 nmol) significantly enhanced memory on the retention test. In Experiment 2, this effect was attenuated by blocking noradrenergic receptors in the amygdala with propranolol (0.3 μg/0.5 μl). Experiment 3 used in vivo microdialysis to determine whether footshock plus glutamate (50.0 nmol) alters noradrenergic output in the amygdala. These treatments caused a significant and long-lasting increase in amygdala noradrenergic concentrations. The results indicate that glutamate may be one transmitter that conveys the effects of vagal activation on brain systems that process memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttrial hippocampal, amygdaloid, and lateral hypothalamic electrical stimulation: Effects on short- and long-term memory of an appetitive experience.

52 Long-Evans male water-deprived rats were given 150 licks of a 10% sucrose solution, followed 4 sec later by 30 sec of low-intensity electrical brain stimulation applied in the dorsal hippocampus, amygdala, or lateral hypothalamus. Retention of the licking experience was then tested either 90 sec of 24 hrs after the lick experience by measuring the number of licks taken on an empty drinking tube. Ss that received hippocampal stimulation licked the empty tube less than the 17 controls did during the 24-hr, but not during the 90-sec, retention test. Data suggest that the hippocampus may be critically involved in processes (e.g., consolidation) mediating long-term, but not short-term, memory. Compared with controls, Ss that received amygdala stimulation did not exhibit any changes in licking at either retention test. Ss given lateral hypothalamic stimulation showed more licking compared with controls during the 90-sec, but not the 24-hr, test. Subsequent tests suggest that facilitation of short-term memory may have been influenced by stimulation-induced motivational changes. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prolonged suppression of human immunodeficiency virus type 1 (HIV-1) viremia in persons with advanced disease results in enhancement of CD4 T cell reactivity to microbial antigens but not to HIV-1 antigens

In rats, the septo-hippocampal system is important for memory encoding. Previous reports indicate that muscimol, a specific GABAergic agonist induces learning and memory deficits when infused into the medial septal area. The basolateral nucleus of the amygdala (BLA) modulates memory encoding in other brain areas, including the hippocampus. To explore the interactions between the septo-hippocampal system and amygdala in memory, we studied the effects of intra-medial septal infusions of muscimol in rats with BLA lesions. Animals received sham surgery or excitotoxic BLA lesions and were given infusions of either vehicle or muscimol (5 nmol) into the medial septal area 5 min prior to training sessions in inhibitory avoidance and water maze tasks. In the inhibitory avoidance task, muscimol-induced memory impairment was potentiated by BLA amygdala lesions. Additionally, in the water maze task, BLA-lesioned rats given muscimol infusions into the medial septal also showed memory impairment. These findings indicate that the MSA interacts with the BLA in the processing of memory storage.     

Norepinephrine release in the amygdala after systemic injection of epinephrine or escapable footshock: contribution of the nucleus of the solitary tract

Several findings based largely on lesions and drug manipulations within the amygdala suggest that norepinephrine (NE) systems in the amygdala contribute to enhancement of memory processes by epinephrine (EPI). However, no studies to date have directly measured changes in the release of NE in the amygdala after EPI injection. In Experiment 1, in vivo microdialysis was used to assess amygdala NE release after systemic injection of saline, EPI (0.1 or 0.3 mg/kg), and administration of an escapable footshock (0.8 mA, 1 s). Both doses of EPI produced a significant elevation in NE release that persisted for up to 60 min. In Experiment 2, the local anesthetic lidocaine (2%) was infused (0.5 microl) into the nucleus of the solitary tract (NTS) immediately before injection of 0.3 mg/kg EPI. The EPI-induced elevation in amygdala NE release observed in Experiment I was attenuated by inactivation of the NTS. These findings indicate that systemic injection of EPI increases release of NE in the amygdala and suggest that the effects are mediated in part by activation of brainstem neurons in the NTS that project to the amygdala.     

The Effects of Peripheral Vagal Nerve Stimulation at a Memory-Modulating Intensity on Norepinephrine Output in the Basolateral Amygdala.

Vagal nerve stimulation (VNS) is known to improve cognitive processing, presumably by affecting activity in central nervous system structures that process recently acquired information. It has long been assumed that these effects are related to stimulation-induced increases of norepinephrine (NE) release in limbic brain structures. The present study examined this hypothesis by administering VNS at an intensity and duration that improves memory and then measuring fluctuations in NE output in the basolateral amygdala (BLA) with in vivo microdialysis. In Experiment 1, VNS caused a 98% increase in NE output relative to baseline. In Experiment 2, methyl atropine was given 10 min before VNS to assess whether stimulation-induced increases in amygdala NE are mediated by afferent or efferent vagal branches. Methyl atropine did not alter NE release in the BLA in comparison with saline. The significance of these findings in understanding how peripheral neural activity modulates limbic structures to encode and store new information into memory is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Endocrine regulation of cognition and neuroplasticity: Our pursuit to unveil the complex interaction between hormones, the brain, and behaviour.

Gonadal and stress hormones modulate neuroplasticity and behaviour. This review focuses on our findings over the past decade on the effects of estrogens and androgens on hippocampal neurogenesis, hippocampus-dependent learning and memory and the effects of reproductive experience in the rodent. Evidence suggests that acute estradiol initially enhances and subsequently suppresses cell proliferation in the dentate gyrus of adult female rodents. Repeated exposure to estradiol modulates hippocampal neurogenesis and cell death in adult female, but not male, rodents while, testosterone and dihydrotestosterone upregulate hippocampal neurogenesis in adult male rodents. Estradiol dose-dependently affects different brain regions involved in working memory (prefrontal cortex, hippocampus), reference memory (hippocampus) and conditioned place preference (amygdala). Pregnancy and motherhood differentially regulate adult hippocampal neurogenesis and spatial working memory in the dam after weaning. These studies and others demonstrate that the female brain responds to steroid hormones differently than the male brain. It is of the upmost importance to investigate the effects on neuroplasticity and behaviour in both the male and the female, particularly when modelling diseases that exhibit sex differences in incidence, etiology or treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drugs acting upon the cyclic adenosine monophosphate/protein kinase A signalling pathway modulate memory consolidation when given late after training into rat hippocampus but not amygdala

Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or in the amygdala were trained in one-trial step-down inhibitory (passive) avoidance using a 0.4 mA footshock. At various times after training (0, 1.5, 3, 6 or 9 h for animals implanted in the hippocampus; 0 or 3 h for those implanted in the amygdala), they received infusions of 8-Br-cAMP (cyclic adenosine monophosphate) (1.25 micrograms/side), SKF38393 (7.5 micrograms/side), SCH23390 (0.5 microgram/side), norepinephrine ClH (0.3 microgram/side), timolol ClH (0.3 microgram/side), 8-HO-DPAT (2.5 micrograms/side), NAN-190 (2.5 micrograms/side), forskolin (0.5 microgram/side) or KT5720 (0.5 microgram/side). Rats were tested for retention 24 h after training. SKF38393 is an agonist and SCH23390 an antagonist at dopamine D1 receptors, timolol is a beta-adrenoceptor antagonist, 8-HO-DPAT is an agonist and NAN-190 an antagonist at 5HT1A receptors, forskolin enhances adenylyl cyclase, and KT5720 inhibits protein kinase A. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory and KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF 38393, noradrenaline and NAN-190 caused memory facilitation, and KT5720, SCH23390, timolol and 8-HO-DPAT caused retrograde amnesia. At 9 h from training, all treatments were again ineffective. When given into the amygdala 0 or 3 h post-training all treatments were ineffective, except for noradrenaline at 0 h, which caused retrograde facilitation. The data agree with the suggestion that in the hippocampus, but not the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h from training, and that this is regulated by D1, beta, and 5HT1A receptors. This correlates with a previous report of increased cAMP levels, protein kinase A activity and P-CREB levels at 3-6 h from training in rat hippocampus in this task. This may be taken to suggest that the hippocampus, but not the amygdala, is involved in the long-term storage of step-down inhibitory avoidance in the rat.     

Neural plasticity and emotional memory

Posttraumatic stress disorder is the pathological replay of emotional memory formed in response to painful, life-threatening, or horrifying events. In contrast, depression is often precipitated by more social context-related stressors. New data suggest that different types of life experiences can differentially impact biochemistry, physiology, anatomy, and behavior at the level of changes in gene expression. Repeated separation of neonatal rat pups from their mother results in many long-lasting alterations in biology and behavior paralleling that in depression, including hypercortisolism. The role of the amygdala in modulating emotional memory is highlighted, as well as some of its unique properties such as metaplasticity (i.e., the differential direction of long-term adaptation, either potentiation or depression) in response to the same input as a function of the prior history of stimulation. The implications of these emerging data on the physiological and molecular mechanisms underlying emotional memory emphasize the particular importance of prevention and early intervention.     

Different temporal profiles of amnesia after intra-hippocampus and intra-amygdala infusions of anisomycin.

Systemic or intra-hippocampal administration of the protein synthesis inhibitor anisomycin generally leads to impairments in memory tested 24 hr or more after training but spares memory for a few hours after training. Thus, amnesia does not appear immediately after training but develops with time, findings most often interpreted as evidence for distinct short- and long-term memory processes. However, time courses for the onset of amnesia vary substantially after treatment with protein synthesis inhibitors. Some of the variability across experiments may reflect task-related differences or, perhaps relatedly, may reflect memory processing mediated by different neural systems. In the present experiments, anisomycin was infused into either the hippocampus or the amygdala 20 min before inhibitory avoidance training. Similar to previous findings, intra-hippocampus injections of anisomycin impaired memory tested 48 hr after training yet spared memory tested 4 hr after training. In contrast, intra-amygdala injections of anisomycin impaired memory tested at 0.5, 4, and 48 hr after training, revealing no evidence for spared memory at short times after training. The distinct temporal properties for amnesia following anisomycin injections into the hippocampus or amygdala may reflect different consequences for memory of perturbations of the neural system in which the manipulation is made. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory systems in the brain and localization of a memory

It is now clear that there are a number of different forms or aspects of learning and memory that involve different brain systems. Broadly, memory phenomena have been categorized as explicit or implicit. Thus, explicit memories for experience involve the hippocampus-medial temporal lobe system and implicit basic associative learning and memory involves the cerebellum, amygdala, and other systems. Under normal conditions, however, many of these brain-memory systems are engaged to some degree in learning situations. But each of these brain systems is learning something different about the situation. The cerebellum is necessary for classical conditioning of discrete behavioral responses (eyeblink, limb flexion) under all conditions; however, in the "trace" procedure where a period of no stimuli intervenes between the conditioned stimulus and the unconditioned stimulus the hippocampus plays a critical role. Trace conditioning appears to provide a simple model of explicit memory where analysis of brain substrates is feasible. Analysis of the role of the cerebellum in basic delay conditioning (stimuli overlap) indicates that the memories are formed and stored in the cerebellum. The phenomenon of cerebellar long-term depression is considered as a putative mechanism of memory storage.     

Use of cryoprecipitates in major surgery on the hemophilic patient

Cerebellar influences on the various substructures in the Papez Circuit are indicated by the following. 1. Anatomical studies indicate that the major midbrain areas to which this circuit projects are : 1) ventral tegmental area; 2) interpeduncular area; and 3) periaqueductal gray areas; and these same areas project back to the limbic system. There are projections to these regions from the cerebellar nuclei, as indicated by terminal degeneration studies which show that cerebellar nuclei connect, mostly by fine fibers, with a continuum of cells located on either side of the midline in the ventral tegmentum of the midbrain. Observations that the cerebellum also projects to the locus ceruleus (NA system) and VTA (DA system) indicate that cerebellar influences can also reach the limbic areas via the catecholamine fiber bundles. 2. Electrophysiological studies indicate that vermiam and fastigial stimulation induce evoked responses in the basolateral amygdala, the hippocampus, and the septum, with latencies to the peak of first wave ranging from 4 to 8 msec and to the second wave of 16-29 msec. Citations from the physiological literature indicate that electrical stimulation of the cerebellum, especially the vermis, can modify a wide range of responses which involve functional activities of either the sympathetic or parasympathetic nervous systems. 3. Studies on electrically induced afterdischarges in the septum, hippocampus, and amygdala indicate that cerebellar stimulation can shorten the duration of or terminate the afterdischarges, and the site of lowest threshold is the midline cortex. Focal cooling of the vermis promotes prolongation of the afterdischarges as does pretreatment of animals with 6-OH dopamine. Chemical lesions in the catecholamine system induced by 6-OH dopamine reduce the effectiveness of the cerebellar stimulation, as do lesions of nucleus fastigii. These data are interpreted to indicate that the cerebellum can exert a tonic suppressor (inhibitory?) influence on substructures within the Papez Circuit. 4. Citations from animal behavioral studies indicate that electrical stimulation of the anterior cerebellum can induce responses such as arousal, predatory attack, and feeding which mimic those obtained by amygdaloid stimulation. Fastigial stimulation can produce drowsiness and EEG changes which resemble the sleep patterns resulting from stimulation of the ventral amygdala.     

Lipopolysaccharide-induced interleukin 8 production by human whole blood is enhanced by epinephrine and inhibited by hydrocortisone

To determine the effect of epinephrine and hydrocortisone on lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) production, human whole blood was stimulated with LPS in the presence or absence of these stress hormones. Epinephrine caused a dose-dependent increase in LPS-induced IL-8 production, which was mediated exclusively via beta-adrenergic receptors, as reflected by the facts that beta (but not alpha) receptor blockade reversed the epinephrine effect and beta (but not alpha) receptor stimulation reproduced the epinephrine effect. Further, elevating cellular cyclic AMP (cAMP) concentrations, a known effect of beta-adrenergic stimulation, by addition of dibutyryl cAMP also enhanced LPS-induced IL-8 production. Epinephrine-induced upregulation of IL-10 production masked an even more pronounced stimulating effect of this hormone on IL-8 synthesis, as indicated by the finding that the extent of IL-8 upregulation was greater in the presence of anti-IL-10 than in the absence of anti-IL-10. Hydrocortisone dose-dependently inhibited LPS-induced IL-8 production and reversed epinephrine-induced enhancement of IL-8 production. Epinephrine and hydrocortisone have opposite effects on IL-8 production, which may be relevant for the understanding of endogenous and therapeutic stress hormone influences on IL-8 mediated inflammation.     

The role and mechanisms of action of glucocorticoid involvement in memory storage

Adrenal steroid hormones modulate learning and memory processes by interacting with specific glucocorticoid receptors at different brain areas. In this article, certain components of the physiological response to stress elicited by learning situations are proposed to form an integral aspect of the neurobiological mechanism underlying memory formation. By reviewing the work carried out in different learning models in chicks (passive avoidance learning) and rats (spatial orientation in the Morris water maze and contextual fear conditioning), a role for brain corticosterone action through the glucocorticoid receptor type on the mechanisms of memory consolidation is hypothesized. Evidence is also presented to relate post-training corticosterone levels to the strength of memory storage. Finally, the possible molecular mechanisms that might mediate the influences of glucocorticoids in synaptic plasticity subserving long-term memory formation are considered, mainly by focusing on studies implicating a steroid action through (i) glutamatergic transmission and (ii) cell adhesion molecules.     

Basolateral amygdala lesions block glucocorticoid-induced modulation of memory for spatial learning.

This study examined the role of the amygdala in mediating the effects of glucocorticoids on spatial memory in rats. Adrenalectomy (ADX) induced 4–5 days prior to training impaired memory in a water-maze spatial task. This effect was reversed by a posttraining injection of dexamethasone (0.3 mg/kg sc) but not by corticosterone (0.3 mg/kg). Lesions of the basolateral (BLA), but not the central (CEA) or the medial (MEA), amygdala blocked the effects of ADX and dexamethasone. ADX also impaired acquisition. CEA, MEA, and BLA lesions blocked the ADX effect on acquisition. In adrenally intact rats, intracerebroventricular posttraining injections of a specific glucocorticoid receptor (GR or Type-ll) antagonist impaired retention, and BLA lesions blocked the effect of the GR antagonist. These findings provide evidence that the BLA is involved in mediating glucocorticoid influences on learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Implications of immediate-early gene induction in the brain following sexual stimulation of female and male rodents

Induction of immediate-early genes (IEGs), such as c-fos, has been widely used to mark the activation of brain regions following different types of sexual stimulation and behavior. A relatively common set of hormone-concentrating basal forebrain and midbrain structures in female and male rodents is activated by copulatory stimulation, in particular, stimulation of sensory nerves that innervate the penis or vagina/cervix, olfactory or pheromonal stimuli, and conditioned sexual incentives. These regions include the preoptic area, lateral septum, bed nucleus of the stria terminalis, paraventricular hypothalamus, ventromedial hypothalamus, medial amygdala, ventral premammillary nuclei, ventral tegmentum, central tegmental field, mesencephalic central gray, and peripeduncular nuclei. Regions that do not contain classic intracellular steroid receptors, such as the ventral and dorsal striatum or cortex, are also activated. IEGs have also been colocalized with cytoplasmic proteins like GnRH and oxytocin, and have been used in conjunction with retrograde tracers to reveal functional pathways associated with different sexual behaviors. Steroid hormones can also alter the ability of sexual stimulation to induce IEGs. Despite the many similarities, some differences in IEG induction between sexes have also been found. We review these findings and raise the question of what IEG induction in the brain actually means for sexual behavior, that is, whether it indicates the perception of sexual stimulation, commands for motor output, or the stimulation of a future behavioral or neuroendocrine event related to the consequences of sexual stimulation. To understand the role of a particular activated region, the behavioral or neuroendocrine effects of lesions, electrical stimulation, drug or hormone infusions, must also be known.