Left Intermediate Medial Hyperstriatum Ventrale Research Articles

Lesions of the Intermediate Medial Hyperstriatum Ventrale Impair Sickness-Conditioned Learning in Day-Old Chicks

Lesion studies show that the intermediate medial hyperstriatum ventrale (IMHV), a forebrain visual association area in chicks, is involved in learning and memory for one-trial passive avoidance and imprinting. We examined the effects of IMHV lesions in a one-trial, nongustatory, sickness-conditioned learning task. This task is similar to passive avoidance and imprinting because all three tasks require the chick to remember visual cues in order to respond correctly. However, sickness-conditioned learning differs from imprinting and passive avoidance because it uses sickness as the aversive stimulus and there is a longer conditioned stimulus-unconditioned stimulus interval (30-min delay compared to seconds). Bilateral IMHV lesions given 24 h before training impaired the ability of the chicks to avoid a bead associated with sickness produced by lithium chloride injection, as did pretraining unilateral left or right IMHV lesions. Post-training IMHV lesions given 1 h after training did not impair avoidance of the test bead in the sickness-conditioned learning task. However, lesioned chicks showed generalized avoidance of all test beads. The pretraining lesion results are similar to those found in imprinting and passive avoidance learning; however, the effects of unilateral IMHV lesions differed. Post-training lesion effects are similar to those found in passive avoidance learning. We propose that both left and right IMHV are necessary for sickness-conditioned learning and that post-training IMHV lesions impair the ability of the chick to learn or remember the association between the color of the bead and the aversive consequences of LiCl injection.

Expression of Fos and Jun Proteins Following Passive Avoidance Training in the Day-Old Chick

It has been shown previously that the immediate-early genes, c-fos and c-jun mRNA are induced in the 1-day-old chick forebrain after one-trial passive avoidance training in which chicks learn to avoid pecking at a bitter-tasting bead. Here, we have studied the expression of their proteins using antibodies to Fos and Jun. Western blotting disclosed two immunoreactive bands for the anti-Fos antibody (47 and 54 kD) and two immunoreactive bands for the anti-Jun antibody (39 and 54 kD). Two hours post-training there was an increase in the number of Fos-positive stained nuclei in right intermediate medial hyperstriatum ventrale (IMHV) (P < 0.01), left IMHV (P < 0.05), right lobus parolfactorius (LPO) (P < 0.025) and left LPO (P < 0.05) of birds trained on the bitter bead compared with controls that had pecked a water-coated bead. Staining for Jun protein was significantly greater in the right LPO of trained chicks (P < 0.01). Other forebrain regions showed no increase over quiet control levels. The findings are discussed in the context of the cascade of events involved in passive avoidance memory consolidation in the day-old chick.

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.

Time-dependent increase in release of arachidonic acid following passive avoidance training in the day-old chick.

We have investigated the role of arachidonic acid, a putative retrograde messenger, in a one-trial aversive learning task in the day-old chick. The left and right intermediate medial hyperstriatum ventrale (IMHV) in the chick forebrain have previously been implicated in the formation of memory for this task. Using an ex vivo technique we have determined the concentrations of various fatty acids liberated from prisms prepared from these brain regions at different time points up to 24 h following passive avoidance training. At 30, 60, and 75 min posttraining the concentration of arachidonic acid, but not of other fatty acids, in prisms prepared from the left IMHV, but not the right IMHV, was enhanced compared with that in chicks trained on a nonaversive water-coated bead. To test whether arachidonic acid liberation from the left IMHV was receptor-stimulated we showed that (a) liberation of endogenous arachidonic acid from homogenate prepared from the left and right IMHV of untrained chicks was stimulated by depolarization with KCl (50 mM) and that (b) glutamate agonists of the NMDA and metabotropic subtypes of glutamate receptor stimulated release of preloaded [14C] arachidonic acid from prisms prepared from the left IMHV but not the right IMHV. These results indicate that arachidonic acid is liberated from the left IMHV following passive avoidance training in the day-old chick and may play a role as a retrograde messenger in this memory task.

Passive avoidance learning in the day-old chick is modulated by GABAergic agents

Injection of drugs directly into the intermediate medial hyperstriatum ventrale (IMHV) of day-old chicks, prior to training on a chrome bead dipped in either the strong aversant methyl anthranilate (MeA), or the weak aversant quinine, allows investigation of the effects of potential amnestic and memory-enhancing agents on retention of a passive avoidance task. Chicks were injected into the left and right IMHV, with either saline or muscimol (GABA agonist), 30 minutes before training on an MeA-coated bead. On test, either 10 min, 30 min or 24 h after training, birds were presented with a dry chrome bead. Normally, trained birds will avoid the test bead; however, significantly more muscimol-injected birds pecked the dry bead than did saline-injected chicks, indicating amnesia in the muscimol-injected birds. In chicks injected bilaterally into the IMHV with bicuculline, a GABA A antagonist, 30 minutes prior to training on a quinine-coated bead, avoidance scores were significantly improved on testing at 24 h compared with saline-injected control chicks, indicating enhanced retention in bicuculline-treated birds. These results suggest a role for the GABAer-gic system in the acquisition and retention of passive avoidance learning in the day-old chick.

Protein kinase inhibitors disrupt memory formation in two chick brain regions

The amnesic effects of protein kinase inhibitors (H-7, HA-156, TFP, W-9, and W-13) on memory formation for a one trial peck-avoidance task in chicks were investigated with bilateral and unilateral injections into either the left or the right intermediate medial hyperstriatum ventrale (IMHV) or the left or right lobus parolfactorius (LPO). All five inhibitors injected bilaterally 5 min pretraining into either the IMHV or LPO or unilaterally into the left IMHV produced amnesia. Unilateral injections into the right IMHV did not produce amnesia. Unilateral injections of W-9 or W-13 into the left but not the right LPO produced amnesia. H-7, HA-156, or TFP did not produce amnesia when injected unilaterally into either the left or right LPO. The time of onset of amnesia produced by injecting TFP and W-13 into the LPO occurred 45 min after training, whereas H-7 produced amnesia significantly later (90 min after training). Amnesia induced by TFP, W-13, and H-7 injected into the LPO occurred significantly later than amnesia produced when these agents were injected into the IMHV. Together these data suggest that the IMHV and LPO process memory sequentially using various protein kinase activities.

MK-801 blockade of Fos and Jun expression following passive avoidance training in the chick.

Training chicks on a one-trial passive avoidance task results in transient up-regulation of the N-methyl-D-aspartate (NMDA) receptor in the left intermediate medial hyperstriatum ventrale (IMHV) of the forebrain 30 min post-training. Injection of the non-competitive NMDA receptor inhibitor, (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten 5,10-imine maleate (MK-801), around the time of training renders chicks amnesic for the task. Training also results in enhanced expression of the immediate early gene (IEG) c-fos in the IMHV. To determine the relationship between NMDA receptor up-regulation and IEG induction during memory formation we have examined the expression of Fos, Jun and their related proteins 2 h following training in the presence/absence of the putative amnestic agent MK-801. Western blotting of IMHV samples revealed two protein bands with immunoreactivity to the Fos antibody at 47 and 54 kDa. Using an antibody to Jun, two immunoreactive bands were revealed at 39 and 54 kDa. All bands were enhanced in the left IMHV following passive avoidance training. Post-training intraperitoneal injections of MK-801 (75 mM) produced amnesia in approximately 50% of the birds when tested 1 h after training. Injection of MK-801 significantly attenuated expression of these proteins in birds rendered amnesic, but not in those that recalled the task. We conclude that NMDA receptor activation precedes immediate early gene expression in the memory formation cascade.

Increases in NMDA receptor binding are specifically related to memory formation for a passive avoidance task in the chick: a quantitative autoradiographic study

One-day-old chicks ( Gallus domesticus) were trained on a one-trial passive avoidance task in which the aversive stimulus was an unpleasant tasting substance, methylanthranilate (MeA). Control birds were presented with a water (W) coated bead. Five minutes after training a group of MeA-trained chicks were given a brief sub-convulsive trans-cranial electric shock, which rendered half amnesic whilst the remainder were able to show recall for the aversive stimulus. Thirty minutes after training birds were killed and quantitative receptor autoradiography was used to determine NMDA sensitive [ 3H] l-glutamate binding in specific regions of the forebrain of: (i) MeA-trained chicks; (ii) water-control chicks; (iii) MeA-trained electroshocked chicks showing recall; and (iv) MeA-electroshocked chicks amnesic for the aversive stimulus. Increases (80% in the left lobus parolfactorius and 67% in the left intermediate medial hyperstriatum ventrale) in NMDA sensitive [ 3H] l-glutamate binding occurred in electro-shocked chicks which showed recall of the aversive experience but were absent in MeA-trained chicks rendered amnesic by electro-shock. The increased binding in electroshocked MeA-trained birds which showed recall was similar to that observed previously in MeA-trained birds (without electroshock), compared to water control birds, whereas binding levels in MeA-trained electroshocked amnesic birds were not different from those of water control birds. These data argue strongly that alterations in binding to glutamate receptor sub-types are specific to memory formation for the passive avoidance task.

3H]MK-801 binding asymmetry in the IMHV region of dark-reared chicks is reversed by imprinting

Glutamate NMDA-type receptor binding in the intermediate medial hyperstriatum ventrale (IMHV) of dark-hatched chicks is lateralized. This lateralization was found to be markedly influenced by imprinting. In dark-reared chicks the binding of the selective ligand [ 3H]MK-801 was two-fold higher in the right IMHV than in the left IMHV. In contrast, imprinted chicks have significantly higher levels of [ 3H]MK-801 binding in the left IMHV region than in the right IMHV. Imprinting results in 2a learning-related increase in NMDA-type receptor binding levels in the left IMHV, whereas [ 3H]MK-801 binding levels in the right IMHV remain unchanged by imprinting. Thus, the plasticity present in the NMDA-type receptor system and associated with imprinting appears to occur in the left hemisphere only.

The effect of a passive avoidance task on the release of amino acids in vitro from the left intermediate medial hyperstriatum ventrale (IMHV) of the day-old chick.

The effect of a passive avoidance task on the release of amino acids in vitro from the left intermediate medial hyperstriatum ventrale (IMHV) of the day-old chick.

Glutamate and imprinting memory: the role of glutamate receptors in the encoding of imprinting memory

Glutamate-sensitive receptors have been implicated in many forms of neural plasticity and learning, including imprinting of chicks. Previous studies have indicated that glutamate binding levels in the left intermediate medial hyperstriatum ventrale (IMHV) region of the chick forebrain increase as a correlate of the acquisition of an imprinting memory; however, it has not been determined whether this is due to an increase in the number of glutamate receptors or to increased receptor affinity. The area specificity of these changes, within the left and right hemisphere, was also unexplored. We have performed Scatchard displacement binding analyses to examine changes in both the number and affinity of glutamate receptors in the left and right hyperstriatum ventrale (HV) and also the left and right archistriatal/lobus parolfactorius (AS/LPO) areas from imprinted and non-imprinted chicks. The results of this study demonstrate lateralised increases in both the number and affinity of glutamate receptors in the left HV area at 7–8 h after imprinting. Significant increases in the affinity, but not the number, of glutamate receptors were found in the left AS/LPO. This suggests that the left AS/LPO, which has previously been shown to be involved in the acquisition of a passive avoidance memory, may also be involved in the formation of an imprinting memory.

Training chicks on a passive avoidance task modulates glutamate-stimulated inositol phosphate accumulation.

The effects of glutamate, N-methyl-D-aspartate (NMDA), (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)-cyclo-hepten 5,10-imine maleate (MK801), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and quisqualate on the accumulation of inositol phosphates (IP) from the breakdown of phosphoinositides in vitro have been studied in tissue prisms derived from a region of the chick forebrain, the intermediate medial hyperstriatum ventrale (IMHV). In prisms from the left IMHV, glutamate stimulated IP accumulation by 10-20%, AMPA by 55% and quisqualate by 650%. These effects were more marked in the right IMHV, where AMPA stimulated IP accumulation by 157% and quisqualate by 920%. MK801 and NMDA had no significant effect on IP accumulation in either hemisphere. The left IMHV is known to be the site of a biochemical cascade resulting in synaptic remodelling following training day-old chicks on a one-trial passive avoidance task. The effect of such training was to reduce glutamate-stimulated accumulation of IP by 27% (P < 0.05) in prisms taken 30 min after training. There was no effect on prisms taken at 5 or 180 min after training, and no effect at any time in the right IMHV. MK801, injected intraperitoneally before training at a concentration known to produce amnesia for the passive avoidance task, abolished the training-induced decrease without itself affecting IP accumulation. Taken in conjunction with pharmacological and autoradiographic evidence, these results indicate that memory formation for the passive avoidance task involves the activation of NMDA receptor channels, but not quisqualate or AMPA receptors, in the left IMHV of the chick 30 min after training.

How chicks make memories: the cellular cascade from c-fos to dendritic remodelling

Training chicks on a one-trial passive avoidance task results in a cellular cascade over the subsequent hours. Phosphorylation of the presynaptic phosphokinase C substrate B-50 is followed by immediate-early gene expression and increased synthesis of pre- and postsynaptic glycoproteins, increases in dendritic spine densities, synapse and synaptic vesicle numbers, and a prolonged increase in neuronal bursting. Many of these effects have been localized to two forebrain regions: the left intermediate medial hyperstriatum ventrale and the lobus parolfactorius. Pretraining lesions in the left intermediate medial hyperstriatum ventrale, or post-training lesions in the lobus parolfactorius result in amnesia. These and related results lead to models of memory storage based on multiple representation by way of synaptic stabilization through glycoprotein synaptic recognition molecules.

Effects of early experience on c- fos gene expression in the chick forebrain

The expression of c- fos mRNA was studied by blot and in situ hybridisation in the forebrains of young chicks subjected to different types of experience-dependent stimulation. Exposure to one hour of activity in a rich visual environment produced a significant increase in forebrain c- fos mRNA in 1-day or 2-day-old chicks; this increase was most marked in cerebellum and medial forebrain - especially intermediate medial hyperstriatum ventrale (IMHV) regions. Levels of c- fos mRNA were not elevated in birds which had been accommodated to the enriched environment for 2 days, suggesting that the novelty of presented stimuli play a critical role in the c- fos induction. Training chicks on a one-trial passive avoidance task was followed by 2- to 2.5-fold increases in c- fos mRNA in both left and right IMHV and lobus parolfactorius (LPO) 30 min after the learning experience. Occlusion of one eye during training resulted in an asymmetrical expression of c- fos in the hemisphere contralateral to the open eye. Therefore c- fos is induced in the chick forebrain during learning and its activation cannot be attributed to ‘stress’, arousal or intensity of sensory stimulation alone. These observations support the hypothesis that c- fos expression in the brain is related to the acquisition of new experience.

Dissociation of brain sites necessary for registration and storage of memory for a one-trial passive avoidance task in the chick.

Although memory formation occurs in a sequence of pharmacologically dissociable stages, many models assume that this sequence is located within a single neuronal ensemble. Three forebrain areas in the young chick-the intermediate medial hyperstriatum ventrale (IMHV), the lobus parolfactorius (LPO), and the paleostriatum augmentatum--have been identified as important structures in mediating learning and memory processes. It has been shown that pretraining lesions placed to the left IMHV produce amnesia for a 1-trial passive avoidance task. Posttraining lesions in the IMHV are not amnestic. The present study demonstrated that bilateral lesions to the LPO are amnestic but only if made subsequent to rather than before training. These results suggest that long-term storage of the memory is dependent on the LPO. Further experiments determined that in the absence of the LPO at training, the right IMHV can act a long-term memory storage site. In the absence of the right IMHV at training, other, as yet undetermined, areas can take up this role.

Memory formation in the chick depends on membrane-bound protein kinase C

The role of protein kinase C (PKC) in the formation of memory for a one-trial passive avoidance task in 1-day-old chicks has been studied, following earlier observations that training on this task results in transient and lateralised changes in the phosphorylation state of presynaptic B-50 protein, a PKC substrate. In accord with hypotheses that the activity of PKC is regulated by translocation from cytosol to membrane, a significant increase was found in the fraction of the α/β forms of the enzyme, assayed immunologically, present in a synaptic-membrane-bound, Triton-extractable form in the left intermediate medial hyperstriatum ventrale (IMHV) of chicks 30 min after training on the passive avoidance task. Two inhibitors of PKC, melittin (10 μl, 120 μM) and H7 (10 μl, 10 mM), if injected intracerebrally 10 min prior to or 10 min after training, were without effect on the general behaviour of the chicks or their training. However, these injections of the inhibitors produced amnesia in birds tested 3 h later. This effect was lateralised; only left hemisphere injections of the inhibitors produced amnesia. A possible state-dependency interpretation of these results was ruled out. The results are discussed in the context of hypotheses as to the regulatory role of PKC in neural plasticity and memory formation.

Pre- and post-training lesions of the intermediate medial hyperstriatum ventrale and passive avoidance learning in the chick

Three distinct nuclei of the chick forebrain--the intermediate medial hyperstriatum ventrale (IMHV), lobus parolfactorius (LPO), and paleostriatum augmentatum (PA)--show metabolic, morphological, and neurophysiological changes following training on a passive avoidance task, suggesting that these and other areas of the chick forebrain participate in memory formation for this task. Considerable evidence exists for lateralization of memory processes in the chick. Several experiments examined the effects of lesions in the IMHV on the ability of chicks to learn and retain the avoidance task. Pre-training bilateral lesions in the IMHV produced an impairment in avoidance responding tested three hours after training. Pre-training unilateral lesions in the left but not the right IMHV resulted in a similar impairment. However, bilateral IMHV ablations, given either 1 or 6 h post-training, did not impair retention. IMHV lesions did not impair retention of a simple escape learning task. These results are consistent with other studies that have examined the effects of bilateral IMHV lesions on acquisition of passive avoidance and extend these findings by demonstrating lateralization of acquisition involving the left IMHV. The results also suggest that, as early as one hour post-training, the IMHV is not necessary to retain the memory and indicate that other forebrain structures, possibly the LPO or PA, may maintain the memory trace following training. Hypotheses to account for these results and indications of future research are discussed.

Training induced dendritic spine density changes are specifically related to memory formation processes in the chick, Gallus domesticus

The density of dendritic spines on large, multipolar, projection neurons in the intermediate medial hyperstriatum ventrale (IMHV) of 1-day-old chicks was examined after training on a one-trial passive avoidance task. Chicks trained on the task were given a brief, subconvulsive transcranial electroshock 5 min after training, a procedure which rendered about half of them amnesic. The spine density was found to be significantly higher 24–26 h after training in the left IMHV in chicks that remembered the response compared to chicks rendered amnesic. These data, taken together with our earlier observations on spine density changes following training, argue strongly in favour of a specific role for dendritic spines in memory formation in the chick.

The role of the uncrossed fibre system in interocular transfer in the rabbit and rat

The expression of c-fos mRNA was studied by blot and in situ hybridisation in the forebrains of young chicks subjected to different types of experience-dependent stimulation. Exposure to one hour of activity in a rich visual environment produced a significant increase in forebrain c-fos mRNA in 1-day or 2-day-old chicks; this increase was most marked in cerebellum and medial forebrain - especially intermediate medial hyperstriatum ventrale (IMHV) regions. Levels of c-fos mRNA were not elevated in birds which had been accommodated to the enriched environment for 2 days, suggesting that the novelty of presented stimuli play a critical role in the c-fos induction. Training chicks on a one-trial passive avoidance task was followed by 2- to 2.5-fold increases in c-fos mRNA in both left and right IMHV and lobus parolfactorius (LPO) 30 min after the learning experience. Occlusion of one eye during training resulted in an asymmetrical expression of c-fos in the hemisphere contralateral to the open eye. Therefore c-fos is induced in the chick forebrain during learning and its activation cannot be attributed to ‘stress’, arousal or intensity of sensory stimulation alone. These observations support the hypothesis that c-fos expression in the brain is related to the acquisition of new experience.