Spatial Working Memory Formation Research Articles

Concurrent interactions between prefrontal cortex and hippocampus during a spatial working memory task.

Spatial working memory (SWM) refers to a short-term system for temporary manipulation of spatial information and requires the cooperation of multiple brain regions. Despite evidence that the hippocampus (HPC) and prefrontal cortex (PFC) are involved in SWM, how the PFC and HPC interact during SWM remains puzzling. In this study, local field potentials (LFPs) were recorded simultaneously from rat ventral HPC and medial PFC during SWM tasks firstly. A cross-frequency coupling algorithm was used to test for functional connectivity in the PFC and HPC. Granger causality (GC) algorithm was used to test for effective connectivity in the PFC and HPC. Finally, concurrent interactions across two brain regions were analyzed based on functional connectivity and effective connectivity. Experimental results show that the LFPs power in the PFC and HPC decreased during the learning period and peaked before the rats' behavioral selection during SWM. Moreover, the LFPs power mainly distributed in theta and gamma that are related to SWM. In relation to the functional connectivity, the effect of activity transmission during SWM in the PFC and HPC is the same; the phase-amplitude coupling (PAC) between gamma in the PFC and theta in the HPC is correlated with the formation of SWM and supports concurrent interactions between the PFC and HPC. In relation to the effective connectivity, the directed activity transmission in the HPC is greater than that in the PFC during SWM, indicating flow of activity from the HPC to the PFC.

Hippocampal Cortactin Levels are Reduced Following Spatial Working Memory Formation, an Effect Blocked by Chronic Calpain Inhibition.

The mechanism by which the hippocampus facilitates declarative memory formation appears to involve, among other things, restructuring of the actin cytoskeleton within neuronal dendrites. One protein involved in this process is cortactin, which is an important link between extracellular signaling and cytoskeletal reorganization. In this paper, we demonstrate that total hippocampal cortactin, as well as Y421-phosphorylated cortactin are transiently reduced following spatial working memory formation in the radial arm maze (RAM). Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression. Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training. These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

Intrahippocampal Norleucine 1-Angiotensin IV mitigates scopolamine-induced spatial working memory deficits

Depletion of cholinergic neurons in the hippocampus has been implicated in memory impairment and Alzheimer's Disease (AD). The brain angiotensin AT 4 receptor is co-localized with cholinergic neurons, and the AT 4 receptor has also been implicated in cognitive processing. The current investigation used the spatial win-shift version of the radial arm maze to determine the involvement of AT 4 receptors in spatial working memory formation. We initially established that intrahippocampal scopolamine significantly impaired the spatial working memory performance of Sprague-Dawley rats in the radial arm maze. We also demonstrated that subsequent intrahippocampal infusions of Norleucine 1-Angiotensin IV (Nle 1-AngIV) significantly prevented the scopolamine-induced deficit. Consistent with previously published data on long-term spatial memory, our findings suggest that activation of AT 4 receptors can compensate for impaired spatial working memory resulting from compromised muscarinic acetylcholine receptor function. We further demonstrate that the hippocampus is a site of action for Nle 1-AngIV-mediated cognitive improvement.

Activity Pattern-Dependent Long-Term Potentiation in Neocortex and Hippocampus of GluA1 (GluR-A) Subunit-Deficient Mice

The AMPA receptor subunit GluA1 (GluR-A) has been implicated to be critically involved in the expression of long-term potentiation (LTP) and memory formation. Mice lacking this subunit possess a profound spatial working memory deficit. We investigated the influence of the GluA1 subunit on the expression of LTP in pyramidal neurons of the hippocampus CA1 region and somatosensory cortex layer 2/3 for different cellular LTP protocols in adult mice. We found that the GluA1 subunit was not required for LTP in cortical pyramidal neurons. In contrast, GluA1-dependent LTP expression in CA1 pyramidal neurons was differentially dependent on the LTP induction parameters. Depolarization pairing was exclusively, theta-burst pairing was partially, and spike-timing-dependent plasticity (STDP) was independent of the GluA1 subunit. Spike-timing-dependent LTP required postsynaptic membrane fusion in CA1 pyramidal neurons. We conclude that during LTP induction at the hippocampal CA3-to-CA1 synapse the recruitment of the GluA1 subunit is controlled by particular electrical activity patterns that might reflect specific behavioral states. Furthermore, other LTP expression mechanisms exist that do not require the presence of GluA1. The previously reported spatial working memory deficits in GluA1-lacking mice (Gria1(-/-) mice) together with these results suggest that STDP might be a likely basis for the formation of spatial reference memory whereas it is not required for the rapid formation of spatial working memory where a fast but transient increase of synaptic efficacy might be needed.

NBQX does not affect learning and memory tasks in mice: a comparison with D-CPPene and ifenprodil

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( F)-quinoxaline (NBQX) did not impair working memory measured as alternation behavior in the Y-maze in mice. No depressant effect on alternation was detected even when NBQX impaired locomotion measured as the total number of arm entries. Similar profile of action in the Y-shaped maze was observed after administration of an anti-ischemic drug ifenprodil. In contrast, the N- methyl- d - aspartate (NMDA) antagonist ( d-(E)-4-(3- phosphonoprop-2- enyl)piperazine-2- carboxylate (D-CPPene) impaired spontaneous alternation. In the step-through passive avoidance task, mice were trained to avoid dark compartment entry. NBQX and ifenprodil did not impair learning in this task when administered before or immediately after training. In contrast, D-CPPene disturbed acquisition when administered before but not immediately after training or before retention test. These observations suggest that AMPA receptors are not critically involved in the formation of spatial working memory and acquisition (storage) in the passive avoidance, and have no effect on recall (retrieval) from long-term memory.