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J Quevedo

Publications and source records attributed to J Quevedo.

At least 55 records · Page 3Linked to original sources
PubMed1998

Local control of information flow in segmental and ascending collaterals of single afferents.

In the vertebrate spinal cord, the activation of GABA(gamma-amino-butyric acid)-releasing interneurons that synapse with intraspinal terminals of sensory fibres leading into the central nervous system (afferent fibres) produces primary afferent depolarization and presynaptic inhibition. It is not known to what extent these presynaptic mechanisms allow a selective control of information transmitted through specific sets of intraspinal branches of individual afferents. Here we study the local nature of the presynaptic control by measuring primary afferent depolarization simultaneously in two intraspinal collaterals of the same muscle spindle afferent. One of these collaterals ends at the L6-L7 segmental level in the intermediate nucleus, and the other ascends to segment L3 within Clarke's column, the site of origin of spinocerebellar neurons. Our results indicate that there are central mechanisms that are able to affect independently the synaptic effectiveness of segmental and ascending collaterals of individual muscle spindle afferents. Focal control of presynaptic inhibition thus allows the intraspinal branches of afferent fibres to function as a dynamic assembly that can be fractionated to convey information to selected neuronal targets. This may be a mechanism by which different spinal postsynaptic targets that are coupled by sensory input from a common source could be uncoupled.

Afferent Pathways↗
PubMed1998

Intrahippocampal infusion of the NMDA receptor antagonist AP5 impairs retention of an inhibitory avoidance task: protection from impairment by pretraining or preexposure to the task apparatus.

The purpose of the present research was to further evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in inhibitory avoidance task consolidation. Adult male Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.4 mA footshock, 24 h training-test interval). Immediately after training, animals received a 0.5-microl intrahippocampal infusion of the NMDA receptor antagonist aminophosphonopentanoic acid (AP5) (5.0 microg) or vehicle (phosphate buffer in saline, pH 7.4). The infusion of AP5 impaired retention test performance. Both pretraining with a low footshock intensity (0.2 mA) or preexposure to the inhibitory avoidance box 24 h before training prevented the amnestic effect of AP5. The results suggest that hippocampal NMDA receptors are critical for neither the enhancement of retention induced by an additional training session nor the inhibitory avoidance retention in animals that have previously learned about the task environment by preexposure to the apparatus.

2-Amino-5-phosphonovalerate↗
PubMed1998

L-type voltage-dependent calcium channel blocker nifedipine enhances memory retention when infused into the hippocampus.

Wistar rats with cannulae bilaterally implanted in the CA1 region of the dorsal hippocampus were trained in a step-down inhibitory avoidance task. Through these cannulae they received an infusion of 28 or 280 ng per side of the L-type voltage-dependent calcium channel antagonist nifedipine, or of its vehicle (20% dimethyl sulfoxide in saline). The two doses of the drug were studied by administration 0 or 30 min after training; in addition, the higher dose was studied by infusion 10 min before training. A retention test was carried out 24 h after the training session. The highest dose of nifedipine administered 0 min post-training enhanced test session performance of the animals compared to the control group; the effect of the lower dose was not statistically significant. There was no effect of the drug given 30 min post-training or 10 min pretraining. Despite the inability to discriminate direct neural from indirect vascular effects, these results are consistent with previous reports on nootropic actions of the dihydropyridine class of calcium channel blockers. The data are at variance with the amnestic effect of intrahippocampal nifedipine described by Lee and Lin (1991, Life Sciences, 48, 1333-1340), which may be attibuted to the different range of doses studied here. This might resemble the inverted U-shaped dose-response curve observed with another dihydropyridine, nimodipine, by other authors.

Animals↗
PubMed1998

Differential involvement of cortical receptor mechanisms in working, short-term and long-term memory.

Rats received, through bilaterally implanted indwelling cannulae, 0.5 microliter infusions of 6-cyano-7-nitroquinoxaline2,3-dione (CNQX) (0.5 microgram), D-2-amino-5-phophono pentanoic acid (AP5) (5.0 micrograms), muscimol (0.5 microgram), scopolamine (2.0 micrograms), SCH23390 (2.5 micrograms), saline or a vehicle into the CA1 region of the hippocampus, or into the antero-lateral prefrontal (PRE), posterior parietal (PP) and entorhinal cortex (EC). The infusions were given 6 min prior to one-trial step-down inhibitory avoidance training in order to measure their effect on working memory (WM), or immediately post-training in order to measure their effect on short-term (STM) and long-term memory (LTM), 1.5 and 24 h later, respectively. WM was inhibited by CNQX or muscimol given into any of the cortical areas, by SCH23390 given into CA1, PRE or PP, and by scopolamine given into PRE or EC. STM was unaffected by any of the treatments given into PRE, and was inhibited by CNQX or muscimol given into CA1, PP and EC and by scopolamine given into PP, and enhanced by SCH given into CA1. LTM was inhibited by CNQX, muscimol, scopolamine or SCH23390 given into PRE, by scopolamine given into PP, by SCH23390 given into the entorhinal cortex, and by AP5, CNQX, muscimol or scopolamine given into CA1. The results indicate a differential involvement of the various neurotransmitter systems in the three types of memory in the various brain areas, and a separation of the mechanisms and of the regions involved in each. In addition, some of the findings suggested links between WM and LTM processing in PRE, between WM and STM processing in EC and PP, and between all three types of memory in CA1.

Animals↗
PubMed1998

Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats.

The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-microliter infusion containing 5.0 microgram of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean +/- SEM number of conditioned responses (CRs) during retention test session was 16.47 +/- 1.78 in the vehicle group and 9.93 +/- 1.59 in the AP5 group; P < 0.05). Post-training infusion of AP5 did not affect retention (mean +/- SEM number of conditioned responses during retention test session was 18.46 +/- 1.94 in the vehicle group and 20.42 +/- 2.38 in the AP5 group; P > 0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory.

2-Amino-5-phosphonovalerate↗
PubMed1998

Interaction between midazolam-induced anterograde amnesia and memory enhancement by treatments given hours later in hippocampus, entorrhinal cortex or posterior parietal cortex.

Rats were bilaterally implanted with indwelling cannulae in the CA1 region of the dorsal hippocampus, the entorrhinal cortex or the posterior parietal cortex. After recovery from surgery, they were trained in a one-trial step-down inhibitory avoidance task using a 0.3 mA footshock. The animals received i.p. 15 min before training either saline (1 ml/kg) or midazolam (1 mg/kg). Three hours after training they received, through the cannulae, infusions of saline, norepinephrine (0.3 microg/side), SKF38393 (7.5 microg/side), or 8-Br-cAMP (1.25 microg/side) into the brain regions mentioned. Animals were tested for retention 24 h after the training session. Midazolam produced anterograde amnesia, and the post-training treatments (with the exception of SKF38393 given into the entorrhinal cortex) caused retrograde memory facilitation. The amnestic effect of midazolam and the facilitatory effect of the treatments given into the brain cancelled each other out. Therefore, the mechanisms triggered by midazolam can interact with others in areas involved in memory processing several hours after their onset.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Further evidence for the involvement of a hippocampal cGMP/cGMP-dependent protein kinase cascade in memory consolidation.

Hippocampal cyclic GMP (cGMP) has been recently postulated to participate in an early phase of memory consolidation of an inhibitory avoidance learning in rats. Here we report on the effects of the intrahippocampal infusion of a soluble guanylyl cyclase inhibitor (LY 83583) in the consolidation of one-trial step-down inhibitory avoidance and on the effect of this task on hippocampal cGMP levels and cGMP-dependent protein kinase (PKG) activity. Bilateral intrahippocampal administration of LY 83583 (2.5 micrograms per side) caused full amnesia for inhibitory avoidance when given immediately (0 min) after training, but not 30 min post-training. Rats submitted to the inhibitory avoidance task showed a significant increase in both cGMP levels and in PKG activity in the hippocampus at 0 min after training. No changes were observed 30 min after training. These findings provide further evidence that the hippocampal cGMP/PKG cascade is involved in the early stages of memory formation of an inhibitory avoidance task in rats.

Aminoquinolines↗
PubMed1997

Systemic administration of ACTH or vasopressin reverses the amnestic effect of posttraining beta-endorphin or electroconvulsive shock but not that of intrahippocampal infusion of protein kinase inhibitors.

Retrograde amnesia was induced in rats trained in step-down inhibitory avoidance by four different treatments: an ip injection of beta-endorphin (1.0 microgram kg), an electroconvulsive shock (ECS), an intrahippocampal infusion of the calcium/calmodulin protein kinase II inhibitor, KN62 (0.08 microgram/side), given 0 h after training, or an intrahippocampal infusion of the protein kinase A inhibitor, KT5720 (0.5 microgram/side), given 3 h after training. Pretest ip injections of ACTH (0.2 microgram/kg) or vasopressin (10.0 micrograms/kg), but not saline, reversed the amnesia caused by beta-endorphin and ECS but not that caused by the enzyme inhibitors. This suggests that the amnesia produced by intrahippocampal KN62 and KT5720 administration is stronger than that caused by ECS and beta-endorphin, possibly because the former interfere directly with specific steps of the core biochemical chain of events that underlies memory consolidation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Selective cortical and segmental control of primary afferent depolarization of single muscle afferents in the cat spinal cord.

This study was primarily aimed at investigating the selectivity of the cortico-spinal actions exerted on the pathways mediating primary afferent depolarization (PAD) of muscle spindle and tendon organ afferents ending within the intermediate nucleus at the L6-L7 segmental level. To this end we analyzed, in the anesthetized cat, the effects produced by electrical stimulation of sensory nerves and of the cerebral cortex on (a) the intraspinal threshold of pairs of single group I afferent fibers belonging to the same or to different hindlimb muscles and (b) the intraspinal threshold of two collaterals of the same muscle afferent fiber. Afferent fibers were classified in three categories, according to the effects produced by stimulation of segmental nerves and of the cerebral cortex. Twenty-five of 40 fibers (62.5%) were depolarized by stimulation of group I posterior biceps and semitendinosus (PBSt) or tibialis (Tib) fibers, but not by stimulation of the cerebral cortex or of cutaneous and joint nerves, which instead inhibited the PBSt- or Tib-induced PAD (type A PAD pattern, usually seen in Ia fibers). The remaining 15 fibers (37.5%) were all depolarized by stimulation of the PBSt or Tib nerves and the cerebral cortex. Stimulation of cutaneous and joint nerves produced PAD in 10 of those 15 fibers (type B PAD pattern) and inhibited the PBSt- or Tib-induced PAD in the 5 remaining fibers (type C PAD pattern). Fibers with a type B or C PAD pattern are likely to be Ib. Not all sites in the cerebral cortex inhibited with the same effectiveness the segmentally induced PAD of group I fibers with a type A PAD pattern. With the weakest stimulation of the cortical surface, the most effective sites that inhibited the PAD of individual fibers were surrounded by less effective sites, scattered all along the motor cortex (area 4gamma and 6) and sensory cortex (areas 3, 2 and 1), far beyond the area of projection of group I fibers from the hindlimb. With higher strengths of cortical stimulation, the magnitude of the inhibition was also increased, and previously ineffective or weakly effective sites became more effective. Maps obtained when using the weakest cortical stimuli have indicated that the most effective regions that produced PAD of group I fibers with a type B or type C PAD pattern were also scattered throughout the sensory-motor cortex, in the same general area as those that inhibited the PAD of group I afferents with a type A PAD pattern. In eight fibers with a type A PAD pattern it was possible to examine the intraspinal threshold of two collaterals of the same single afferent fiber ending within the intermediate nucleus at the L7 segmental level. In six fibers, stimulation of the PBSt nerve with trains of pulses between 1.5 and 1.86 times threshold (xT) produced a larger PAD in one collateral than in the other. In seven fibers, stimulation of the sensory-motor cortex and of cutaneous nerves produced a larger inhibition of the PBSt-induced PAD in one collateral than in the other. The ratio of the cortically induced inhibition of the PAD elicited in the two collaterals could be modified by changing the strength of cortical and of PBSt stimulation. In three fibers it was possible to inhibit almost completely the background PAD elicited in one collateral while having little or no effect on the PAD in the other collateral. Changes in the intraspinal threshold of pairs of collaterals following electrical stimulation of segmental nerves and of the somato-sensory cortex were examined in three fibers with a type B and two fibers with a type C PAD pattern. In four fibers the PAD elicited by stimulation of cutaneous (4-20xT) and muscle nerves (1.54-3.7xT), or by stimulation of the sensory-motor cortex, was of different magnitude in the two collaterals. In two experiments it was possible to find cortical sites in which weak surface stimulation produced PAD in one collateral only. (ABSTRACT TRUNCATED)

Action Potentials↗
PubMed1997

Patterns of connectivity of spinal interneurons with single muscle afferents.

A technique was developed to measure, in the anesthetized and paralyzed cat under artificial ventilation, changes of excitability to intraspinal stimulation simultaneously in two different afferent fibers or in two collaterals of the same afferent fiber. Intraspinal stimulation reduced the threshold of single muscle afferent fibers ending in the intermediate nucleus. This effect was seen with strengths below those required to activate the afferent fiber tested (1.5-12 microA), occurred at a short latency (1.5-2.0 ms), reached a maximum between 15 and 30 ms, and lasted up to 100 ms. The effects produced by graded stimulation applied at the shortest conditioning-testing stimulus time intervals increased by fixed steps, suggesting recruitment of discrete elements, most likely of last-order interneurons mediating primary afferent depolarization (PAD). The short-latency increases in excitability produced by the weakest effective intraspinal stimuli were usually detected only in the collateral closest to the stimulating micropipette, indicating that the stimulated interneurons mediating PAD have spatially restricted actions. The short-latency PAD produced by intraspinal stimuli, as well as the PAD produced by stimulation of the posterior biceps and semitendinosus (PBSt) nerve or by stimulation of the bulbar reticular formation (RF), was depressed 19-30 min after the i.v. injection of 0.5 mg/kg of picrotoxin, suggesting that all these effects were mediated by GABAergic mechanisms. The PAD elicited by stimulation of muscle and/or cutaneous nerves was depressed following the i.v. injection of (-)-baclofen, whereas the PAD elicited in the same collateral by stimulation of the RF was baclofen-resistant. The short-latency PAD produced by intraspinal stimulation was not always depressed by i.v. injections of (-)-baclofen. Baclofen-sensitive and baclofen-resistant monosynaptic PADs could be produced in different collaterals of the same afferent fiber. The results suggest that the intraspinal terminals of single muscle afferents receive synapses from more than one PAD-mediating GABAergic interneuron and that a single last-order interneuron has synaptic connections with a restricted number of intraspinal terminals and/or collaterals of the same afferent fiber. In addition, they support the existence of separate subsets of last-order baclofen-sensitive and baclofen-resistant interneurons that respond predominantly to segmental and to descending inputs. It is suggested that the restricted nature of the PAD plays an important role in the central control of the synaptic effectiveness of group I muscle afferents.

Afferent Pathways↗
PubMed1997

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.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

The N-methyl-D-aspartate receptor blocker MK-801 prevents the facilitatory effects of naloxone and epinephrine on retention of inhibitory avoidance task in rats.

The aim of this study was to evaluate the interaction between N-methyl-D-aspartate (NMDA) receptors and the adrenergic and opioid systems in the modulation of inhibitory avoidance retention. Rats were trained and tested in the step-down inhibitory avoidance task (0.3 mA footshock). The training-test interval was 24 h. The animals received an i.p. injection of saline or MK-801 (0.0625 mg/kg) 30 min before training, and saline, epinephrine (25 micrograms/kg), or naloxone (0.4 mg/kg) i.p. immediately after training. In the saline-pretreated rats, epinephrine and naloxone enhanced memory retention. Pretraining MK-801 prevented the facilitatory effects of those treatments. The present findings suggest that the facilitation of learning by post-training epinephrine and naloxone is prevented by the pretraining NMDA receptor blockade.

Adrenergic Agonists↗
PubMed1997

Involvement of mechanisms dependent on NMDA receptors, nitric oxide and protein kinase A in the hippocampus but not in the caudate nucleus in memory.

The effects of the NMDA receptor antagonist AP5, the nitric oxide synthase (NO) inhibitor NO-arg or the protein kinase A (PKA) inhibitor KT5720 on memory were evaluated. Rats bilaterally implanted in the CA1 region of the dorsal hippocampus were trained and tested in a step-down inhibitory avoidance task, and rats unilaterally implanted in the left posteroventral region of the caudate nucleus were trained and tested in a cued water maze task. Previous findings from this and other laboratories had found that lesions or pharmacological treatments of these sites significantly altered memory of these two tasks. Immediately after training, animals received intrahippocampal or intracaudate 0.5 microliter microinfusions of saline, AP5, NO-arg or KT5720. All three drugs impaired retention of inhibitory avoidance, but did not affect retention of the cued water maze. The findings suggest that NMDA receptor-, NO- and PKA-mediated processes in the dorsal hippocampus, but not in the caudate nucleus, are involved in memory.

2-Amino-5-phosphonovalerate↗