The amygdala and emotional memory.
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Amygdala↗
Biomedical subjects
J L McGaugh
Publications and source records attributed to J L McGaugh.
Footshock facilitates the expression of aversively motivated memory in rats given post-training amygdala basolateral complex lesions.
We previously reported that increased training in an escape task partially attenuates the memory impairment produced by large amygdala lesions induced 1 week following training. The present study examined the effect of amount of preoperative training on the retention of rats with lesions restricted to the amygdala basolateral complex. Rats received 1 or 10 training trials in a footshock-motivated escape task and 1 week later sham lesions or neurotoxic lesions of the basolateral complex. Four days after recovery from the surgery they were tested for inhibitory avoidance retention and then 2 days later given continuous multiple trial inhibitory avoidance training (CMIA) in the same apparatus. The basolateral complex lesions significantly decreased the retention latencies of rats given 1 or 10 trials. However, following administration of footshock on the CMIA task, the performance of the lesioned rats reflected the degree of preoperative escape training. The basolateral complex lesions also increased open field locomotor activity, an effect that may have contributed to the shorter retention latencies in lesioned animals. These findings indicate that an intact amygdala basolateral complex is not critical for the retention of the escape training.
Amygdala↗
Differential involvement of the right and left amygdalae in expression of memory for aversively motivated training.
The present study investigated possible lateralization of amygdala involvement in memory for aversively motivated training. Rats with bilateral cannulae aimed at the amygdalae were trained in a one-trial inhibitory avoidance task. Twenty-four h or 10 days later, animals received bilateral pre-test microinjections of either vehicle, 2% lidocaine, or unilateral infusions of each simultaneously. Five min after the infusions, retention was tested. Retention latencies of rats given bilateral lidocaine or unilateral lidocaine into only the right amygdala were significantly lower than controls. These results suggest that the right and left amygdalae may make differential contributions to the expression of memory, and that the contribution of the right amygdala may be more important to the expression of memory for aversively motivated training.
Amygdala↗
Memory impairment induced by intraamygdala beta-endorphin is mediated by noradrenergic influences.
These experiments examined the effects on memory in two tasks, inhibitory avoidance and water-maze spatial learning, of intraamygdala injections of drugs affecting noradrenergic and opiate receptors. Male Sprague-Dawley rats (180 g, 50 days old on arrival) were given either a single training trial in an inhibitory avoidance task or eight trials in a water-maze task in which they were trained to swim to a platform submerged 1 cm below the water surface and located in a constant position. Intra-amygdala injections of beta-endorphin (0.03 or 0.1 ng), clenbuterol (10 or 30 ng), or propranolol (0.3 microgram) were given alone or concurrently: beta-endorphin (0.1 ng) + clenbuterol (10 or 30 ng) or beta-endorphin (0.03 ng) + propranolol (0.3 microgram). The injections (0.5 microliter) were administered immediately after inhibitory avoidance training and 5 min before water-maze training. Inhibitory avoidance retention was tested 48 h after training and water-maze retention was tested 24 h after training. In both tasks, clenbuterol attenuated the retention impairing effect of beta-endorphin. Also, in both tasks, low doses of beta-endorphin (0.03 ng) and propranolol (0.3 microgram), which did not affect retention when administered alone, impaired retention when administered concurrently. These results are consistent with extensive previous evidence suggesting that opioid and noradrenergic systems interact in modulating memory storage and provide additional support for the view that the interaction is due to opioid inhibition of noradrenergic activation within the amygdala.
Amygdala↗
Muscimol induces retrograde amnesia for changes in reward magnitude.
These experiments examined the effect of the GABAA agonist, muscimol (MUS), on memory for changes in reward magnitude. In Experiment 1 rats were trained to run a straight alley for either a large or small food reward. After reaching asymptotic performance rats in the high reward group were shifted to the small food reward. Half the animals received 1.0 or 3.0 mg/kg (ip) of MUS or the equivalent volume of saline immediately after training. Shifted training continued for 3 more days and no further injections were given. Shifted saline animals displayed an increase in response latencies compared to unshifted controls with a sharp peak on the day after the shift. Shifted MUS receiving 1.0 mg/kg performed comparably to shifted saline animals. In contrast, Shifted MUS animals receiving 3.0 mg/kg displayed performance comparable to shifted saline animals on the day of the shift but displayed a sharp increase in response latencies on the second day after the shift. These findings indicate that post-training systemic MUS injections delay the peak increase in response latencies and suggest that MUS induces retrograde amnesia for reward reduction. Experiment 2 examined the effect of MUS on the memory of a reward increase. Rats were first trained as in Experiment 1 and rats under the high reward condition were then shifted to the small reward. On the next training session, the large food reward was reinstated.(ABSTRACT TRUNCATED AT 250 WORDS)
Amnesia, Retrograde↗
Differential effects of pretraining inactivation of the right or left amygdala on retention of inhibitory avoidance training.
Rats with bilateral cannulas aimed at the amygdalae received bilateral infusions of either buffer or lidocaine hydrochloride, or unilateral infusions of each, 5 min before continuous multiple-trial inhibitory avoidance (CMIA) training. Retention was tested 48 hr later. Some of the rats were retrained at this time and tested again 48 hr later. Bilateral infusions of lidocaine prior to the initial training impaired acquisition, retention, and relearning of the CMIA task. Unilateral infusions of lidocaine into the right or left amygdala did not affect acquisition. Rats given lidocaine into the right amygdala were impaired on retention 48 hr later. The findings are consistent with others indicating involvement of the amygdala in acquisition and consolidation of aversively motivated learning and suggest possible differential involvement of the right and left amygdalae in memory consolidation.
Amygdala↗
Spared retention of inhibitory avoidance learning after posttraining amygdala lesions.
Previous findings indicate that the memory-impairing effects of posttraining amygdala lesions are attenuated by increasing the number of training trials given prior to the induction of the lesion. The aim of this experiment was to determine whether the degree of impairment is also influenced by the footshock intensity used during training. Rats were given 1 trial of inhibitory avoidance (IA) training with either no footshock or a footshock at 1 of 3 intensities. Sham or neurotoxic amygdala lesions were induced 1 week later. On a retention test performed 4 days after surgery, the performance of all amygdala-lesioned rats given footshock training, including those given the lowest training footshock, was better than that of amygdala-lesioned rats given no training footshock. These findings of preserved retention of IA learning in rats given posttraining amygdala lesions do not support a general hypothesis that the amygdala is a locus of permanent changes underlying aversively motivated learning.
Amygdala↗
Muscimol infused into the medial septal area impairs long-term memory but not short-term memory in inhibitory avoidance, water maze place learning and rewarded alternation tasks.
These experiments investigated the effects of injections of muscimol (1 or 5 nmol), administered into the medial septal area prior to training, on memory tested at different retention delays after training in 3 tasks: an inhibitory avoidance task, a one-trial place learning task, and a rewarded alternation task. In all 3 tasks, intraseptal injections of muscimol did not impair memory performance at short retention delays, but impaired memory at the longer retention delays. These findings are consistent with the view that GABAergic regulation of the septohippocampal cholinergic system plays a selective role in the establishment of long-term memory.
Animals↗
Effects of intra-amygdala injections of NMDA receptor antagonists on acquisition and retention of inhibitory avoidance.
These experiments examined the effects of intra-amygdala injections of NMDA receptor antagonists on the acquisition and retention of inhibitory avoidance. In Expt. I, rats received bilateral intra-amygdala injections of the NMDA antagonists D,L-AP5 (1-10 micrograms), D-AP5 (0.03-1 micrograms), CPP (0.125 or 0.375 microgram), or MK-801 (0.2 or 0.5 microgram) prior to training in a continuous multiple-trial inhibitory avoidance (CMIA) task. Acquisition of the task was not significantly affected by any of the drug injections. In contrast, all three competitive antagonists, D,L-AP5, D-AP5 and CPP, produced dose-dependent impairment of 48 h retention performance. Although the MK-801 injections did not significantly impair retention performance, the retention scores of the 0.5 microgram MK-801 group were bimodally distributed, indicating retention impairment in a subgroup of the animals given that dose. Intra-amygdala injections of 3 or 10 micrograms D,L-AP5 did not affect footshock sensitivity (Expt. II) or locomotor activity (Expt. III) and their retention-impairing effects were not due to induction of state dependency (Expt. IV). The retention-impairing effects of intra-amygdala injections of NMDA antagonists were not due to diffusion of the drugs dorsally: injections of 1 microgram D-AP5 into the striatal area directly above the amygdala impaired acquisition but not retention performance (Expt. V). The retention-impairing effects of 1 microgram D-AP5 or 0.5 microgram MK-801 were attenuated by giving additional training to the animals shortly after receiving intra-amygdala injections (Expt. VI). The implications of these findings for hypotheses concerning amygdala function in learning and memory are discussed.
Amygdala↗
Basolateral amygdala lesions block diazepam-induced anterograde amnesia in an inhibitory avoidance task.
This experiment examined the effects of diazepam (DZP) on acquisition and retention of an inhibitory avoidance response by rats with excitotoxic-induced lesions of central (CE), lateral (LAT), or basolateral (BL) amygdala nuclei. Sham-operated and lesioned rats received i.p. injections of DZP (2.0 mg per kg of body weight) 30 min before training in a continuous multiple-trial inhibitory avoidance task. Retention was tested 48 h later. Acquisition was not impaired by the lesions or the DZP. Retention was impaired in animals with CE and LAT lesions in comparison with sham-operated controls. DZP impaired retention in the sham-operated controls as well as CE- and LAT-lesioned animals but did not affect retention in animals with BL lesions. These findings indicate that the DZP-induced anterograde amnesia for inhibitory avoidance training is mediated through influences involving the BL amygdala nucleus.
Amnesia↗
Memory-enhancing effects of post-training dipivefrin and epinephrine: involvement of peripheral and central adrenergic receptors.
These experiments examined the effects, in mice, of post-training i.p. injections of dipivefrin (DPE), a lipophilic prodrug of epinephrine, and epinephrine (EPI) on 48-h retention assessed in inhibitory avoidance and Y-maze discrimination tasks. DPE, in doses of 0.3-10 micrograms/kg significantly facilitated retention: the effects were approximately 10-fold more potent than those of EPI obtained with similar experimental conditions. The alpha-adrenergic antagonists prazosin (alpha 1; 3.0 mg/kg; i.p.), yohimbine (alpha 2; 3.0 mg/kg; i.p.) and phentolamine (alpha 1 and alpha 2; 3.0 mg/kg; i.p.) did not block the enhancement of retention induced by either DPE (10.0 micrograms/kg; i.p.) or EPI (0.1 mg/kg; i.p.). However, the beta-adrenergic antagonist propranolol (2.0 mg/kg; i.p.) attenuated the effects of both DPE and EPI. Sotalol (2.0 mg/kg; i.p.), a peripherally-acting beta-adrenergic antagonist, attenuated the effects of EPI but not those of DPE. These findings suggest the DPE-induced enhancement of memory involves central beta- but not alpha-adrenergic mechanisms while EPI's effects are initiated by activation of peripheral beta-adrenergic systems.
Adrenergic Antagonists↗
Reversible inactivation of the nucleus of the solitary tract impairs retention performance in an inhibitory avoidance task.
Several peripherally acting hormones and drugs are known to modulate memory storage processes, yet the mechanisms which permit these agents to influence memory is not well understood since they do not freely enter the brain. The nucleus of the solitary tract (NTS) is one brainstem structure which receives important neural input from the periphery. Therefore, the objective of this experiment was to determine whether the NTS is involved in modulating processes contributing to memory formation. Male Sprague-Dawley rats were trained in a one-trial inhibitory avoidance task (0.35 mA, 0.5 s footshock). Immediately or 2 h after training microinjections of 2% lidocaine hydrochloride (20 mg/kg) or a phosphate buffer solution were administered bilaterally into the NTS. Two other groups received microinjections of lidocaine into the fourth ventricle or cerebellum. On retention tests given 48 h after training the latency to reenter the dark compartment of the apparatus was recorded. The retention latencies of rats receiving bilateral microinjections of 0.5 microliter of lidocaine hydrochloride into the NTS were significantly shorter than those of animals given injections of a buffer solution (0.5 microliter), delayed injections of buffer or lidocaine, or control injections of lidocaine into the cerebellum or fourth ventricle. These findings suggest that memory storage processes are impaired by reversible inactivation of the NTS after training. The implications of these findings in terms of a possible role of the NTS in modulating brain processes involved in memory storage are discussed.
Amygdala↗
Double dissociation of fornix and caudate nucleus lesions on acquisition of two water maze tasks: further evidence for multiple memory systems.
The present study examined the effect of lesions of the caudate nucleus or fimbria-fornix on the acquisition of two water maze tasks. In both tasks, two rubber balls with different visual patterns were used as platforms (i.e., cues). The "correct" cue was attached to a submerged rectangular platform and could be mounted by an animal to escape the water. The "incorrect" cue was attached to a thin round pedestal and could not be mounted. In a spatial version of the task, the correct cue was located in the same quadrant of the maze on all trials, whereas the visual pattern on the cue was varied from trial to trial. Lesions of the fornix, but not the caudate nucleus, impaired acquisition of this spatial task in relation to control animals. In a simultaneous visual discrimination version of the task, the correct cue on all trials was one with a specific visual pattern, and the spatial location of the correct cue was varied from trial to trial. Lesions of the caudate nucleus, but not the fornix, impaired acquisition of this visual discrimination task in relation to control animals. The double dissociation observed supports the hypothesis that the hippocampus and caudate nucleus are parts of systems that differ in the type of memory they mediate.
Animals↗
Increased training in an aversively motivated task attenuates the memory-impairing effects of posttraining N-methyl-D-aspartate-induced amygdala lesions.
This study was designed to examine the effect of variations in the amount of preoperative training on the retention deficit produced by posttraining lesions of the amygdaloid complex (AC). Rats received 1, 10, or 20 training trials in a footshock-motivated escape task 7 days before receiving N-methyl-D-aspartate lesions of the AC. Inhibitory avoidance retention performance, which was measured 4 days postoperatively, indicated that increased training improved retention in AC-lesioned animals as well as in control animals. The retention performance of AC-lesioned animals was impaired when compared with that of controls; however, the impairment was partially attenuated by increased preoperative training. The finding that AC-lesioned animals displayed greater locomotor activity on the retention test compared with nonlesioned controls suggests that the increased activity may have contributed to the impaired inhibitory avoidance retention performance. Two days after the retention test, some of the AC-lesioned animals were subsequently trained on a continuous multiple-trial inhibitory avoidance response in the same apparatus. AC lesions did not block acquisition or retention of the task. These findings suggest that the amygdala may not be a critical site for the permanent changes mediating stimulus-affect associations based on extensive training.
Amygdala↗
Amygdala lesions block the amnestic effects of diazepam.
This experiment examined the effects of pre-training systemic injections of the benzodiazepine (BZ) diazepam (DZP) on learning and retention of an inhibitory avoidance response in rats with bilateral lesions of the amygdaloid complex (AC) induced by intra-amygdala injections of the excitotoxin N-methyl-D-aspartic acid (NMDA). Unoperated, sham-operated and AC-lesioned rats received i.p. injections of DZP (1.0 or 2.0 mg/kg) or vehicle 30 min prior to training in a continuous multiple-trial inhibitory avoidance task. Retention was tested 48 h later. The acquisition and retention of the AC-lesioned rats were impaired, relative to that of the unoperated and sham controls. In the unoperated and sham controls, DZP impaired retention but did not affect acquisition. In contrast, in animals with AC lesions, DZP did not affect either acquisition or retention. These findings suggest that the amnestic effects of DZP are mediated, at least in part, through influences involving the AC.
Amnesia↗
Norepinephrine-induced plasticity and one-trial olfactory learning in neonatal rats.
The influence of norepinephrine (NE) on the acquisition of a conditioned odor preference and enhanced focal uptake of [14C]2-deoxyglucose (2-DG) within the olfactory bulb was assessed in neonatal rat pups. On postnatal day (PN) 6, pups were injected with either an NE receptor agonist (isoproterenol), NE receptor antagonist (propranolol or timolol), or saline before one-trial odor conditioning. The experimental conditioning group received a 10-min exposure to an odor (peppermint) and reinforcing tactile stimulation similar to that received from the dam. Control groups received only the odor, only the tactile stimulation, backwards presentation of the odor and tactile stimulation or neither of these stimuli. The next day, pups were either tested for an olfactory preference (Expts. 1 and 2) or assessed for differential olfactory bulb activity using the 2-DG technique (Expt. 3). The results indicate that early odor experience with either tactile stimulation or isoproterenol is sufficient to produce a learned behavioral preference and enhanced focal 2-DG uptake within the olfactory bulb. Moreover, an NE receptor blocker injected prior to training with odor and tactile stimulation blocks the acquisition of both behavioral preference and the enhanced 2-DG uptake. In Expt. 4, the effects of tactile stimulation and isoproterenol were further assessed. An odor paired with a moderate level of either of these stimuli produces learning. However, the simultaneous presentation of a moderate level of these stimuli paired with an odor does not result in an odor preference. An odor preference may be reinstated by simultaneous presentation of these stimuli, provided the level of each of these stimuli is too low to produce an odor preference when presented alone with an odor. These data suggest that exogenous NE and tactile stimulation are additive in their effect on learning. These results are discussed in terms of the neural mechanisms underlying reinforcement in infant rats.
Animals↗
Reversible inactivation of the insular cortex by tetrodotoxin produces retrograde and anterograde amnesia for inhibitory avoidance and spatial learning.
Tetrodotoxin (TTX; a voltage-sensitive sodium channel blocker) was microinjected bilaterally into the insular (IC), frontal (FC), or parietal (PC) cortex or the ventral caudate nucleus of rats either before or after they were trained in an inhibitory avoidance task. When administered either before or after training, injections of TTX into the IC impaired performance on a 48-hr retention test. Injections of TTX into the PC also impaired retention when administered before training. One week later, rats with cannulae in the IC, FC, and PC received microinjections of TTX either before or after training in a water maze (Morris) spatial learning task and retention was tested 24 hr later. TTX impaired retention when administered to the IC either before or after training. These findings indicate that a functionally intact IC during and after training in these tasks appears to be essential for the storage of long-term memory.
Amnesia↗
Amygdala and dorsal hippocampus lesions block the effects of GABAergic drugs on memory storage.
These experiments examined the effects of posttraining systemic administration of the GABAergic agonist muscimol and the GABAergic antagonist bicuculline on retention in mice with bilateral lesions of the amygdala, dorsal hippocampus or caudate nucleus. Unoperated male CD1 mice and mice with either sham lesions or electrolytically induced lesions of these 3 brain regions were trained in a one-trial inhibitory avoidance task and, immediately after training, received i.p. injections of either muscimol, (1.0, 2.0 or 3.0 mg/kg), bicuculline, (0.25, 0.5 or 1.0 mg/kg), or control solutions. Retention was tested 24 h after training. Lesions of the 3 brain regions produced comparable impairment of retention. In the unoperated controls and sham controls muscimol and bicuculline produced dose-dependent impairment and enhancement, respectively, of retention. The drug effects on retention were blocked by lesions of the amygdala and hippocampus, but were not blocked by lesions of the caudate nucleus. These findings are consistent with other recent evidence suggesting that the amygdala and hippocampus are involved in mediating posttraining neuromodulatory influences on memory storage.
Amygdala↗