[Show abstract][Hide abstract] ABSTRACT: Evidence suggests that the NO/sGC/PKG pathway plays a key role in memory processing but the actual participation of this signaling cascade in the amygdala during memory consolidation remains unknown. Here, we show that when infused in the amygdala immediately after inhibitory avoidance training, but not later, the NO synthase inhibitor L-NNA hindered long-term memory retention without affecting locomotion, exploratory behavior, anxiety state or retrieval of the avoidance response. The amnesic effect of L-NNA was not state-dependent and was mimicked by the soluble guanylyl cyclase inhibitor LY83583 and the PKG inhibitor KT-5823. On the contrary, post-training intra-amygdala infusion of the NOS substrate L-Arg, the NO-releasing compound SNAP or the non-hydrolysable analog of cGMP 8Br-cGMP increased memory retention in a dose-dependent manner. Co-infusion of 8Br-cGMP reversed the amnesic effect of L-NNA and LY83583 but not that of KT-5823. Our data indicate that the NO-induced activation of PKG in the amygdala is a necessary step for consolidation of inhibitory avoidance memory.
Neurobiology of Learning and Memory 11/2008; 91(3):266-72. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The dorsolateral and medial prefrontal cortex are critical for immediate memory processing. The possibility has been raised that those two areas may also contribute to long-term memory formation. Here, we studied the role of specific receptors in dorsolateral and medial prefrontal cortex in immediate and in long-term memory formation of one-trial inhibitory avoidance. Four different specific receptor ligands were infused into these two areas: the dopamine D1 receptor antagonist, SCH23390, the GABA(A) receptor agonist, muscimol, the AMPA glutamatergic receptor antagonist, ciano-nitro-quinoxaline-dione (CNQX), and the NMDA glutamatergic receptor antagonist, aminophosphonovaleric acid (AP5). In all cases the doses used had been previously shown to affect immediate or long-term memory. In the experiments on immediate memory the drugs were given 5 min before training and the animals were tested 3s post-training. These animals were then also tested 24h later for long-term memory. The effect of the treatments on long-term memory was studied by their infusion 0, 90, 180 or 270 min post-training, testing the animals 24h after training. Immediate memory was inhibited by SCH23390, muscimol and CNQX, but not by AP5, given into any of the two subregions. Long-term memory formation was inhibited by SCH23390, muscimol and CNQX, but not by AP5, given pre-training or 0, 90 or 180 but not 270 min post-training into the dorsolateral region; or 90 but not 0 or 180 min post-training into the medial region. Thus, there is a time- and receptor-dependent correlation in the two areas between their role in immediate and in long-term memory processing. Both roles require intact glutamate AMPA and dopamine D1 receptors, are inhibited by GABAergic synapses, and are unaffected by AP5. In the dorsolateral prefrontal cortex the link between immediate and long-term memory appears to be direct; in the medial area the link suffers a 90 min delay.
Neurobiology of Learning and Memory 10/2007; 88(2):160-6. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two major memory systems have been recognized over the years (Squire 1987): the declarative memory system, which is under the control of the hippocampus and related temporal lobe structures, and the procedural or habit memory system, which is under the control of the striatum and its connections. Most if not all learning tasks studied in animals, however, involve either the performance or the suppression of movement; this, if learned well, may be viewed as having become a habit. It is agreed that memory rules change from their first association to those that take place when the task is mastered. Does this change of rules involve a switch from one memory system to another? Here we will comment on: 1) reversal learning in the Morris water maze (MWM), in which the declarative or spatial component of a task is changed but the procedural component (to swim to safety) persists and needs to be re-linked with a different set of spatial cues; and 2) a series of observations on an inhibitory avoidance task that indicate that the brain systems involved change with further learning.
Anais da Academia Brasileira de Ciências 10/2006; 78(3):515-23. · 0.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The brain renin-angiotensin system (RAS) is involved in learning and memory, but the actual role of angiotensin II (A(II)) and its metabolites in this process has been difficult to comprehend. This has been so mainly due to procedural issues, especially the use of multi-trial learning paradigms and the utilization of pre-training intracerebroventricular infusion of RAS-acting compounds. Here, we specifically analyzed the action of A(II) in aversive memory retrieval using a hippocampal-dependent, one-trial, step-down inhibitory avoidance task (IA) in combination with stereotaxically localized intrahippocampal infusion of drugs. Rats bilaterally implanted with infusion cannulae aimed to the CA1 region of the dorsal hippocampus were trained in IA and tested for memory retention 24 h later. We found that when given into CA1 15 min before IA memory retention test, A(II), but not angiotensin IV or angiotensin(1-7) induced a dose-dependent and reversible amnesia without altering locomotor activity, exploratory behavior or anxiety state. The effect of A(II) was blocked in a dose-dependent manner by the A(II)-type 2 receptor (AT(2)) antagonist PD123319 but not by the A(II)-type 1 receptor (AT(1)) antagonist losartan. By themselves, neither PD123319 nor losartan had any effect on memory expression. Our data indicate that intra-CA1 A(II) hinders retrieval of avoidance memory through a process that involves activation of AT(2) receptors.
Hormones and Behavior 09/2006; 50(2):308-13. · 3.74 Impact Factor