Trial Passive Avoidance Task Research Articles

The roles of RNA synthesis and protein translation during reconsolidation of passive-avoidance learning in the day-old chick

This series of experiments investigated the role of protein translation and RNA synthesis on consolidation and reconsolidation of passive avoidance learning (PAL) in day-old chicks. Although it is well established that protein translation is required after a reminder, there are conflicting reports in the literature concerning the requirement for RNA synthesis at this time. Day-old male New Hampshire × White Leghorn chicks were trained on a single trial passive avoidance task. The results confirmed the requirement for protein translation during reconsolidation with memory deficits induced by anisomycin (ANI) (10 mg/kg) detected at 60 min post-reminder. It was also established that RNA synthesis was required for consolidation of PAL through inhibition by 5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) (0.075 µg/kg), administered at or after training. The same dose of DRB was also found to inhibit memory post-reactivation. However injections were required before the reminder trial and memory deficits were evident by 60 min, consistent with that found for ANI post-reminder. As with ANI, the DRB-induced memory deficit post-reminder was also transient, and resolved by 24 h post-reminder. For both reconsolidation drug studies, the memory deficit was wholly dependent on the memory being reactivated by a reminder-trial. The study highlights an important role for RNA synthesis following memory reactivation.

Ouabain does not impair reconsolidation following a reminder of passive avoidance learning in the day-old chick

This study investigated the effect of ouabain, an inhibitor of NA(+) and K(+) ATPase, on consolidation and reconsolidation of a passive avoidance learning task in the day-old chick. In the consolidating trace, ouabain is thought to inhibit an intermediate-term memory phase, some aspects of which acts as a "trigger" for long-term stabilisation of the trace by new protein synthesis. It was hypothesised that a similar process may initiate the protein synthesis observed following reminder-activated reconsolidation in the young chick. Chicks were trained on a single trial passive avoidance task. A dose of 0.2 ug/kg ouabain was administered intracranially either 5 min post-training (consolidation processes) or 5 min post-reminder (reconsolidation processes). Consistent with previous research, ouabain administration induced a memory deficit following the initial learning trial. However, contrary to expectation, ouabain did not disrupt memory processing post-reactivation. This finding provides further evidence for the notion that consolidation and reconsolidation are associated with similar, but distinct, stages of processing.

Polyinosinic:polycytidylic acid induces memory processing deficits in the day-old chick

Anecdotal and experimental evidence has demonstrated that humans and animals exhibit physiological and cognitive alterations in response to sickness and injury. It is now clear that these changes are due to the actions of proinflammatory cytokines. The current study examined the effects of peripheral administration of polyinosinic:polycytidylic acid, a synthetic double-stranded viral RNA, on the memory processes of day-old chicks trained on a single trial passive avoidance task. Polyinosinic:polycytidylic acid impaired performance on the passive avoidance task in a dose-dependent manner. Maximal deficits were observed when 5 g/kg polyinosinic:polycytidylic acid was administered 120 min before training. Tests for retention revealed that interference in memory consolidation appeared between 30 and 40 min after training. These results indicate an inhibitory effect of polyinosinic:polycytidylic acid on the processes of memory formation at the transition from intermediate-term memory phase (A) to intermediate-term memory phase (B) of the Gibbs and Ng model of memory formation. The study also investigated the pyrogenic actions of polyinosinic:polycytidylic acid, and examined the effect of pretreatment with ketoprofen, a cyclooxygenase inhibitor. Significant rises in body temperature were observed 30 min after injection of polyinosinic:polycytidylic acid. Inhibition of cyclooxygenase by ketoprofen ameliorated the polyinosinic:polycytidylic acid-induced deficits in retention and attenuated the increase in body temperature. These results demonstrate that polyinosinic:polycytidylic acid induces memory processing deficits and is pyrogenic in the day-old chick and that these effects are cyclooxygenase-dependent.

Pharmaco-behavioural evidence indicating a complex role for ryanodine receptor calcium release channels in memory processing for a passive avoidance task

Calcium signalling is an important process underlying neuronal function and consequently behaviour. The release of calcium from intracellular stores via the ryanodine receptor calcium release (RyR) channel has been implicated in both synaptic plasticity and to a limited extent in memory processing. While past investigations have suggested a role for RyR channels in long-term memory, the present study suggests their action is more complex. Using a single trial passive avoidance task developed for the day-old chick, it is proposed that RyR channels are necessary both prior to the expression of long-term memory and also in retrieval processes. Specifically, 5 mM dantrolene (a specific RyR channel blocker) resulted in a persistent retention loss from 40 min post-training while 10 nM dantrolene produced a transient retention loss centred at 40 min post-training. We speculate that in the context of memory formation, RyR channels may be activated by nitric oxide and in the context of memory retrieval may lead to the activation of large conductance calcium-activated potassium BK Ca channels which, when blocked by 50 nM iberiotoxin, also demonstrated a transient retention loss centred at 40 min post-training.

Zaprinast consolidates long-term memory when administered to neonate chicks trained using a weakly reinforced single trial passive avoidance task

A weakly reinforced variant of the single trial passive avoidance task developed for the day-old chick typically fails to consolidate long-term memory. However, administration of zaprinast, a phosphodiesterase (PDE) type 5 inhibitor, (ic; 10 μl/side) immediately post-training resulted in a dose-dependent increase in retention at test 180 min post-training. Further, 100 μM zaprinast resulted in high levels of retention at test 180 min post-training when administered from 10 min before training to 10 min after training. Finally, 100 μM zaprinast, when administered immediately post-training, resulted in the consolidation of long-term memory at a number of times of test extending as late as 24 h post-training. Inhibition of PDE type 5 is known to increase cellular cGMP levels. Previous investigations using a strongly reinforced variant of this task have suggested a role for cGMP in memory retrieval, we now postulate that cGMP is also necessary for memory formation in chicks trained using passive avoidance.

Inhibition of endogenous carbon monoxide production induces transient retention losses in the day-old chick when trained using a single trial passive avoidance learning task

Carbon monoxide (CO) is most often thought of as an exogenous toxin rather than as a possible endogenous nootrope. However, a limited number of studies have suggested that CO is necessary in memory processing for at least some tasks. While nitric oxide (NO) and CO are known activators of guanylyl cyclase (GC), only the effect of NO on GC has been extensively investigated as a mechanism underlying memory processing. The aim of the present study was to determine if inhibition of CO production would have an effect on memory processing. Using chicks trained on a single trial passive avoidance task, inhibition of CO production using zinc (II) deuteroporphyrin IX 2,4-bis ethylene glycol (ZnBG; 5 μM) resulted in two transient retention losses occurring at around 40 and 130 min post-training. The timing of these transient retention losses was similar to those observed following inhibition of GC, using the same species and task in a previous study. This supports the notion that CO is necessary in memory processing for this task and may act through a GC-dependent mechanism. As ZnBG also directly inhibits GC or nitric oxide synthase (NOS) at high concentrations, a second experiment was carried-out to confirm the specificity of ZnBG for heme oxygenase (HO) at the concentration used. The action of ZnBG was challenged with the HO agonist hemin (100 μM) and the transient deficits were abolished. This confirmed that the action of ZnBG on memory was through a CO-related mechanism rather than directly on GC or NOS. In this way the specificity of ZnBG (5 μM) for HO could be confirmed. The results support a role for endogenous CO in memory processing, possibly through activation of GC. In addition, the transient retention losses observed following administration of ZnBG suggest that CO may be necessary for memory retrieval and not formation as previously thought.

The effects of the dopamine D1 receptor antagonist SCH23390 on memory reconsolidation following reminder-activated retrieval in day-old chicks

This series of experiments examined the involvement of the dopamine D1 receptor antagonist, SCH23390, on memory reconsolidation following reminder-activated retrieval. Day-old male New Hampshire × White Leghorn chicks were trained on a single trial passive avoidance task. A dose of 0.5 mg/kg of SCH23390 was administered subcutaneously 5 min before reminder trials, which were presented at 30, 60, and 90 min following training. Memory deficits were observed when reminder trials were presented at 30 and 60 min following training, but not when a reminder was presented at 90 min. No effect on memory retention was observed when reminder trials were not presented, suggesting that reconsolidation mechanisms were both contingent on the presentation of the reminder and independent of the consolidation process. Following a reminder presented at 60 min post-training, deficits in memory retention emerged between 45 and 60 min. The deficit was prolonged, lasting for up until 48 h after reminder presentation. The results indicate an important role for the D1 receptor in reconsolidation processes.

A scavenger of peroxynitrite prevents long-term memory formation using a single trial passive avoidance task for the day-old chick

The important role of nitric oxide (NO) in memory processing has been recognised for some time. However, the mechanisms through which NO may act are only partially understood. One highly reactive radical brought about by the reaction of NO and superoxide ions is peroxynitrite. The current study investigated the effect of peroxynitrite scavenging on retention for a single trial passive avoidance task developed for the day-old chick. Administration of a range of concentrations of the peroxynitrite scavenger Trolox (0.1 μM–1.2 mM) yielded a bimodal retention curve. This dose–response curve had nadirs at 300 and 800 μM. A time of administration study was conducted for each optimal concentration of Trolox and in both studies, the effective range of administration times extended from at least 10 min before training to 20 min post-training. Finally, a retention function was conducted for each optimum concentration of Trolox and in both studies a persistent retention loss was observed from 40 min post-training until the conclusion of the experiment 24 h post-training. The findings suggest that physiological levels of peroxynitrite may be required for the consolidation of long-term memory in this model of memory formation. Interestingly, the effective times of administration and time of retention loss onset are consistent with previous studies which blocked NO synthesis. Therefore it may be suggested that NO acts to facilitate long-term memory formation through the production of peroxynitrite.

God's organism? The chick as a model system for memory studies.

The young chick is a powerful model system in which to study the biochemical and morphological processes underlying memory formation. Training chicks on a one trial passive avoidance task results in a molecular cascade in a specific brain region, the intermediate medial hyperstriatum ventrale. This cascade is initiated by glutamate release and engages a series of synaptic transients including increased calcium flux, up-regulation of NMDA-glutamate receptors, membrane protein phosphorylations, and the retrograde messenger NO. Expression of immediate early genes c-fos and c-jun precedes the synthesis, glycosylation, and redistribution, >4 hr downstream, of a number of synaptic membrane proteins, notably NCAM and L1. Other membrane proteins required in the early phase of memory formation include the amyloid precursor protein (APP) and apolipoprotein E. There are concomitant increases in dendritic spine number and changes in synaptic structure. Nonsynaptic factors, including corticosterone and BDNF, can modulate retention of the avoidance response, enhancing the salience of otherwise weakly retained memory. These results are discussed in relation to general concepts of memory formation and the spatio-temporal distribution of the putative memory trace.

Changes in phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in processing of short-term and long-term memories after passive avoidance learning.

Characteristic autophosphorylation of calcium/ calmodulin-dependent protein kinase II (CaMKII) and its consequences have made this kinase an interesting target in studying the molecular pathway for important neuronal functions including learning and memory formation. In this article, we use immunoprecipitation and immunoblotting methods to detect changes in phosphorylation of CaMKII during memory formation in 1-day-old chicks trained in a single trial passive avoidance task. A 60-kDa protein has been immunoprecipitated from the chick brain with an anti-rabbit CaMKII antibody. This protein shows strong and specific immunoactivities with antibodies against the calmodulin binding site of CaMKII, and the N and C terminals of beta-CaMKII. Commercially available anti-phosphoserine and anti-phosphothreonine antibodies are shown to sensitively detect phosphorylation of purified CaMKII. The basal phosphorylation of CaMKII from the intermediate medial hyperstriatum ventrale (IMHV) and lobus parolfactorius (LPO) regions of the chick brain is shown to be largely right hemisphere-lateralized. When chicks are subjected to a passive avoidance training experience, a specific increase in CaMKII phosphorylation is induced in the IMHV and LPO of the left hemisphere from those chicks whose memory for the training experience is successfully retrieved. While this specific increase in CaMKII phosphorylation is seen in both the left IMHV and left LPO in short-term memory, it is detectable only in the left LPO associated with long-term memory retrieval. The present results provide evidence that in vivo changes in phosphorylation of CaMKII are associated specifically with processing of distinct memory stages, which take place in specific brain regions.

Brief Retention Deficits Associated with Cyclically Recurring Left Hemisphere Events

In the chick, brief episodes of enhanced recall (“retrieval events”) recur approximately every 25 min in recall via the right hemisphere, and every 16 min in recall via the left. These events coincide with, and probably cause, the numerous transitions between memory phases described in the chick.; The most important of these is the transition to long-term memory, which is sometimes held to occur in chicks at about 50 min after learning, a transition picked out as unique by a variety of effects of amnesia-inducing agents, and by a brief impairment (“dip”) in recall at 55 min. We used a single trial passive avoidance task, involving bead pecking, to show that in chicks using only one eye, such dips occur not only at 55 min (in right-eyed chicks only) but also after each of the subsequent series of left hemisphere events (in left-eyed chicks only). Dips in recall appear to result when processes that are initiated by left hemisphere retrieval events result in hemispheric interaction, with one hemisphere (which can be either left or right) holding an inadequate trace (e.g., as a result of monocular training). Recall tests under such conditions may involve both the adequate and the inadequate trace, so that performance is impaired.

Double dissociation between the effects of muscarinic antagonists and benzodiazepine receptor agonists on the acquisition and retention of passive avoidance.

Both muscarinic antagonists, such as scopolamine, and benzodiazepine receptor (BZR) agonists, such as diazepam, produce a reliable impairment in the performance of one trial passive avoidance. Such deficits are frequently interpreted as drug-induced amnesia. However, these deficits could also result from a learning impairment. The present experiments compared the effects of two BZR agonists, lorazepam (0, 0.125, 0.25, and 0.375 mg/kg, IP) and diazepam (0, 0.78, 1.56, and 3.13 mg/kg, IP) with the effects of two muscarinic antagonists, scopolamine (0, 0.6, 0.8 and 1.0 mg/kg, SC) and atropine (0, 15, 30 and 60 mg/kg, IP) on a multiple trial passive avoidance task. In this procedure, the rats were trained with a 5-min inter-trial interval until a learning criterion was achieved. Retention was assessed 24 h later. This enabled the effects of the drugs on the acquisition and the retention of a passive avoidance response to be dissociated. Both atropine and scopolamine produced a marked impairment in the acquisition of the passive avoidance response, but did not impair retention. In contrast, diazepam and lorazepam did not alter the acquisition of a passive avoidance response, but did produce a dose-dependent impairment of retention. These results therefore demonstrate a double dissociation between the effects of muscarinic antagonists and BZR agonists on the acquisition and retention of passive avoidance.

The impairment of long-term memory formation by the phosphatase inhibitor okadaic acid

While there is considerable evidence that protein kinase activity is involved in memory formation, there has been, as yet, no direct investigation of a role for protein phosphatases. However, phosphatases have been implicated in the effects of the activation of glutamate receptors of the NMDA type, in long-term depression, and in the regulation of transmitter release and membrane ion channel activities, phenomena which have been shown to be possibly involved in cellular memorial processes. In the present paper, inhibition of protein phosphatase by 0.5 nM okadaic add, a selective inhibitor of phosphatases 1 and 2A, is demonstrated to prevent memory consolidation in day-old chicks trained on a single trial passive avoidance task. Retention losses first occurred after 30 min post-learning at an intermediate stage of memory formation preceding a protein synthesis-dependent long-term stage. It Is suggested that protein phosphatase activity is involved in precursor processes to long-term memory consolidation.

Astrocytes implicated in the energizing of intermediate memory processes in neonate chicks

Day-old chicks trained in a single trial passive avoidance task develop three sequentially dependent stages of discrimination memory. The second intermediate stage is made up of two phases: the initial A phase being susceptible to inhibition of oxidative metabolism in the tricarboxcylic acid (TCA) system with 2,4-dinitrophenol (DNP), and a second DNP-insensitive B phase. The studies reported in this paper found that doses of the metabolic toxins fluoroacetate (0.2 mM) and fluorocitrate (0.1 mM) previously reported to disrupt the astrocytic TCA cycle only, also disrupt the A (but not the B) phase of intermediate memory, suggesting an interaction between the astrocytic and neuronal oxidative systems may be required to meet the metabolic demands of this earlier phase. The B phase, on the other hand, was not expressed in the presence of the glycolytic inhibitor iodoacetate (1 mM), suggesting that glycolysis (known to be more efficient in astrocytes) and glycogenolysis (which may be exclusive to astrocytes) may support this second phase of intermediate memory. In this regard, the rise in forebrain noradrenaline levels previously reported to occur before the appearance of the B phase is particularly relevant. Given that noradrenaline has been shown to be capable of enhancing glycogenolysis in astrocyte-enriched cell cultures, it is conceivable that noradrenaline exerts an effect on memory by stimulating the glycolytic system in astrocytes, thereby providing energy or metabolites (e.g. pyruvate) needed to sustain the cellular processes operating during the B phase of intermediate memory.

Possible involvement of brain somatostatin in the memory formation of rats and the cognitive enhancing action of FR121196 in passive avoidance task

Using the passive avoidance learning task in rats, the role of brain somatostatin in cognitive function was investigated with special reference to that of the brain cholinergic system. In addition, the involvement of both the brain somatostatinergic and cholinergic systems in the anti-amnesic action of a newly introduced cognitive enhancer, FR121196 [N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide], was examined. Treatment with cysteamine (50, 100, 200 mg/kg, s.c.), a depletor of somatostatin, significantly and dose-dependently reduced the retention of single trial passive avoidance task. Similar memory impairments were found in rats which received central cholinergic blockade either by scopolamine (0.1–1 mg/kg) or by lesioning of the nucleus basalis magnocellularis (NBM). Intracerebroventricurally (i.c.v.) administered somatostatin (1–14) (10–1000 ng/rat) significantly ameliorated the memory impairments induced not only by cysteamine (200 mg/kg) but also by scopolamine (1 mg/kg) and NBM-lesioning. Although physostigmine (0.01–1 mg/kg) also ameliorated the memory impairments induced by cysteamine and scopolamine, it failed to affect the memory impairment seen in the NBM-lesioned rats. Administration of FR121196 (0.1–10 mg/kg) significantly ameliorated the memory deficits produced by scopolamine and NBM lesioning but not that induced by cysteamine. Neurochemical examinations showed that administration of cysteamine significantly reduced the contents of somatostatin but not the choline acetyltransferase activities in all the brain areas examined. These results suggest that the brain somatostatin plays an important role in the cognitive function of rats, and appears to be involved in the cognitive enhancing action of FR121196. Furthermore, the cholinergic neurons degenerated by NBM-lesion may be necessary for the memory enhancement by physostigmine but not for that by somatostatin or FR121196.

Possible noradrenergic involvement in training stimulus intensity

Day-old chicks trained on a single trial passive discrimination avoidance task using a concentrated chemical aversant, methyl anthranilate (MeA), have been shown to exhibit three stages of memory processing: short, intermediate and long term. A similar learning task with the aversant diluted to 20% in ethanol leads to short- and intermediate-term memory only, but not to long-term memory. The emergence of long-term memory has been shown to be associated with the production of a nonenergy-dependent phase of the intermediate memory stage. Subcutaneous administration of propanolol proved capable of inhibiting this nonenergy-dependent phase of memory under a number of training regimes: strongly reinforced training, and with weakly reinforced training presented twice or coupled with a selected dose of the stress-related hormone ACTH. This study supports the notion that there is a phase of memory that occurs prior to the protein synthesis-dependent phase of memory which is susceptible to interference by drugs affecting noradrenergic processes and which may be associated with the intensity of the training stimulus.

Evidence for an anti-amnesic effect of JO 1784 in the rat: a potent and selective ligand for the sigma receptor

JO 1784 ((+)- N-Cyclopropyl-methy- N-methyl-1,4-diphenyl-1,4-diphenyl-1-yl-but-3-en-1-ylamine, hydrochloride), has been recently described as a selective ligand for the sigma receptor with an IC 50 of 39 ± 8nM 28. In the present study the effects of JO 1784 on experimental induced amnesia were investigated using one trial passive avoidance task in rats. Amnesia was produced by injecting scopolamine (1 mg/kg i.p.) 30 min before the second session (T2) on day 2 of the passive avoidance task. The anti-amnesic effect of JO 1784 was compared with other typical and atypical psychotropic drugs which interact at the sigma and or the phencyclidine site. JO 1784 was studied at 5 doses; 0.0625, 0.25, 1.0, 4.0 and 16.0 g/kg i.p. ((+)-3-(3-hydroxyphenyl)- N-1-(prpoyl)piperidine(if(+)-3-PPP)), Rimcazole,(+)- N-allylnormetazocine ((+)-NANM), 1,3-di(2-tolyl) guanidine (DTG) were studied at 4 doses; 0.25, 1.0, 4.0 and 8.0 mg/kg i.p. All drugs were administered 60 min before the test (T2) on day 2 i.e. 30 min before scopolamine. Piracetam (1000 mg/kg p.o.) administered in the same test conditions was used as a reference compound in each experiment. Of the drugs investigated JO 1784 (0.25, 1.0, 4.0 and 16.0 mg/kg i.p.), (+)-3-PPP (0.25, 1.0 and 4.0 mg/kg i.p.), DTG (1.0, 4.0 and 8.0 mg/kg) and piracetam significantly reversed scopolamine induced amnesia on day 3 (T3). At the lower dose, JO 1784 (0.0625 mg/kg) failed to reverse the amnesic effects of scopolamine on day 3. These results suggest that JO 1784 the selective sigma ligand, may be beneficial in amnesic status.

Effects of nucleus basalis magnocellularis lesions on timm-staining in the rat fronto-parietal cortex

Using the passive avoidance learning task in rats, the role of brain somatostatin in cognitive function was investigated with special reference to that of the brain cholinergic system. In addition, the involvement of both the brain somatostatinergic and cholinergic systems in the anti-amnesic action of a newly introduced cognitive enhancer, FR121196 [N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide], was examined. Treatment with cysteamine (50, 100, 200 mg/kg, s.c.), a depletor of somatostatin, significantly and dose-dependently reduced the retention of single trial passive avoidance task. Similar memory impairments were found in rats which received central cholinergic blockade either by scopolamine (0.1–1 mg/kg) or by lesioning of the nucleus basalis magnocellularis (NBM). Intracerebroventricurally (i.c.v.) administered somatostatin (1–14) (10–1000 ng/rat) significantly ameliorated the memory impairments induced not only by cysteamine (200 mg/kg) but also by scopolamine (1 mg/kg) and NBM-lesioning. Although physostigmine (0.01–1 mg/kg) also ameliorated the memory impairments induced by cysteamine and scopolamine, it failed to affect the memory impairment seen in the NBM-lesioned rats. Administration of FR121196 (0.1–10 mg/kg) significantly ameliorated the memory deficits produced by scopolamine and NBM lesioning but not that induced by cysteamine. Neurochemical examinations showed that administration of cysteamine significantly reduced the contents of somatostatin but not the choline acetyltransferase activities in all the brain areas examined. These results suggest that the brain somatostatin plays an important role in the cognitive function of rats, and appears to be involved in the cognitive enhancing action of FR121196. Furthermore, the cholinergic neurons degenerated by NBM-lesion may be necessary for the memory enhancement by physostigmine but not for that by somatostatin or FR121196.

Chronic infusion of GABA and saline into the nucleus basalis magnocellularis of rats: II. Cognitive impairments

In order to assess sensorimotor and/or cognitive modifications following chronic inhibition of nucleus basalis magnocellularis (NBM) neurons, rats trained in two radial maze paradigms (the classical version of the test and a modified version introducing a one-hour delay between the fourth and the fifth choice) received chronic infusion of γ-aminobutyric acid (GABA) into the NBM area. GABA (10 and 50 μg/μl/h) was infused for 3 days into the NBM contralateral to their preferred turning direction in the radial maze. Simultaneously, saline (NaCl 0.9%; 1 μl/h) was infused into the contralateral NBM. GABA and saline infusions were alternated for the subsequent 3-day period. One week later, we investigated the rats' ability to learn a multiple trial passive avoidance task. At the dose of 50 μg/μl, GABA infusion produced (1) a turning bias ipsilateral to the side first infused with GABA, (2) transitory cognitive impairments in radial maze tasks and (3) a deficit in the acquisition of the passive avoidance task. At the dose of 10 μg/μl, the same behavioral deficits were observed except that (1) the turning bias was reversed by the contralateral GABA infusion and (2) cognitive impairments in the radial maze were observed only when a delay was inserted between the fourth and the fifth choice. Histologically, we found a dose-dependent gliosis in the NBM area first infused with GABA. These data suggest a reactivity of the NBM to GABAergic manipulations and the intervention of this structure in both sensorimotor and cognitive processes involved in the radial maze paradigms.

Inhibition of memory in the chick using a monoclonal anti-Thy-1 antibody

One-day-old chicks trained on a single trial passive avoidance task were administered a monoclonal anti-chick Thy-1 antibody, either intracranially or subcutaneously, at various times before and after learning and retention tested at various times post-learning. This procedure resulted in profound amnesia when anti-Thy-1 antibody was administered immediately before learning (5 min) in the case of the subcutaneous injections or 5 min before until 5 min after the learning process with intracranial injections. Antibody administered at other times, either before or after learning had little or no effect on retention. Retention levels were normal until 50 min post-learning, then declined sharply and remained at control levels for the duration of the test period. Chicks injected with anti-chick cerebellum or anti-rat Thy-1 antibodies showed no evidence of amnesia for the concentration of the antibodies used.