Engagement of the PFC in consolidation and recall of recent spatial memory.

The standard model of system consolidation proposes that memories are initially hippocampus dependent and become hippocampus independent over time. Previous studies have demonstrated the involvement of the medial prefrontal cortex (mPFC) in the retrieval of remote memories. The transformations required to make a memory undergo system's consolidation are thought to require synaptic plasticity. In this study, we investigated the participation of the mitogen-activated protein kinase (MAPK)/ERK pathway in acquisition, memory consolidation, and recent memory recall of the Morris water maze (MWM) task using a 1-d training protocol. To this end, bilateral injections of the MEK inhibitor U0126 into the rat mPFC were performed. The injection of the MEK inhibitor in the mPFC did not affect the acquisition of the MWM. However, MEK inhibitor resulted in impairments on recent memory retrieval either when applied at the end of the learning phase (memory consolidation) or prior to the retention test. The results strongly support the concept that recently acquired and consolidated spatial memories require the mPFC, and that local activation of the MAPK/ERK pathway in the mPFC is necessary for the consolidation and recall of recent memories.

[1]  Eric R Kandel,et al.  ERK Plays a Regulatory Role in Induction of LTP by Theta Frequency Stimulation and Its Modulation by β-Adrenergic Receptors , 1999, Neuron.

[2]  April E Hebert,et al.  A role for the prefrontal cortex in recall of recent and remote memories , 2006, Neuroreport.

[3]  James L. McClelland,et al.  Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. , 1995, Psychological review.

[4]  L. Squire,et al.  Retrograde amnesia and memory consolidation: a neurobiological perspective , 1995, Current Opinion in Neurobiology.

[5]  B. Bontempi,et al.  Sites of Neocortical Reorganization Critical for Remote Spatial Memory , 2004, Science.

[6]  Larry R Squire,et al.  Hippocampus and remote spatial memory in rats , 2005, Hippocampus.

[7]  J. David Sweatt,et al.  Activation of p42 Mitogen-activated Protein Kinase in Hippocampal Long Term Potentiation* , 1996, The Journal of Biological Chemistry.

[8]  Sarah E. London,et al.  Functional identification of sensory mechanisms required for developmental song learning , 2008, Nature Neuroscience.

[9]  J. Sweatt,et al.  Mitogen-activated protein kinases in synaptic plasticity and memory , 2004, Current Opinion in Neurobiology.

[10]  J. Sweatt,et al.  The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory , 2001, Journal of neurochemistry.

[11]  B. Bontempi,et al.  Time-dependent reorganization of brain circuitry underlying long-term memory storage , 1999, Nature.

[12]  Bruno Bontempi,et al.  The Formation of Recent and Remote Memory Is Associated with Time-Dependent Formation of Dendritic Spines in the Hippocampus and Anterior Cingulate Cortex , 2009, The Journal of Neuroscience.

[13]  P. Dash,et al.  A Role for Prefrontal Cortex in Memory Storage for Trace Fear Conditioning , 2004, The Journal of Neuroscience.

[14]  Min Zhuo,et al.  Roles of NMDA NR2B Subtype Receptor in Prefrontal Long-Term Potentiation and Contextual Fear Memory , 2005, Neuron.

[15]  Paul W Frankland,et al.  Involvement of the Anterior Cingulate Cortex in the Expression of Remote Spatial Memory , 2006, The Journal of Neuroscience.

[16]  P. Dash,et al.  A Mitogen-Activated Protein Kinase Cascade in the CA1/CA2 Subfield of the Dorsal Hippocampus Is Essential for Long-Term Spatial Memory , 1999, The Journal of Neuroscience.

[17]  J. Sweatt,et al.  Molecular psychology: roles for the ERK MAP kinase cascade in memory. , 2002, Annual review of pharmacology and toxicology.

[18]  D Marr,et al.  Simple memory: a theory for archicortex. , 1971, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[19]  J. Sweatt,et al.  A necessity for MAP kinase activation in mammalian spatial learning. , 1999, Learning & memory.

[20]  W. Scoville,et al.  Loss of Recent Memory After Bilateral Hippocampal Lesions , 2000 .

[21]  J. Seamans,et al.  Selective Roles for Hippocampal, Prefrontal Cortical, and Ventral Striatal Circuits in Radial-Arm Maze Tasks With or Without a Delay , 1997, The Journal of Neuroscience.

[22]  J. D. Bruin,et al.  A behavioural analysis of rats with damage to the medial prefrontal cortex using the morris water maze: evidence for behavioural flexibility, but not for impaired spatial navigation , 1994, Brain Research.

[23]  Alcino J. Silva,et al.  Molecular and cellular cognitive studies of the role of synaptic plasticity in memory. , 2003, Journal of neurobiology.

[24]  R. Morris.  Developments of a water-maze procedure for studying spatial learning in the rat , 1984, Journal of Neuroscience Methods.

[25]  P. Frankland,et al.  The organization of recent and remote memories , 2005, Nature Reviews Neuroscience.

[26]  M Moscovitch,et al.  Hippocampal complex and retrieval of recent and very remote autobiographical memories: Evidence from functional magnetic resonance imaging in neurologically intact people , 2001, Hippocampus.

[27]  Alcino J. Silva,et al.  Stability of recent and remote contextual fear memory. , 2006, Learning & memory.

[28]  Alcino J. Silva,et al.  The Involvement of the Anterior Cingulate Cortex in Remote Contextual Fear Memory , 2004, Science.

[29]  J. D. Bruin,et al.  Pretraining or previous non-spatial experience improves spatial learning in the Morris water maze of nucleus basalis lesioned rats , 2004, Behavioural Brain Research.

[30]  R. Clark,et al.  Reversible hippocampal lesions disrupt water maze performance during both recent and remote memory tests. , 2006, Learning & memory.

[31]  Alcino J. Silva,et al.  New Circuits for Old Memories The Role of the Neocortex in Consolidation , 2004, Neuron.

[32]  P. Cohen,et al.  Specificity and mechanism of action of some commonly used protein kinase inhibitors , 2000 .

[33]  S. Yehuda,et al.  The use of the Morris Water Maze in the study of memory and learning. , 1989, The International journal of neuroscience.

[34]  Alcino J. Silva,et al.  α-CaMKII-dependent plasticity in the cortex is required for permanent memory , 2001, Nature.

[35]  R. Huganir,et al.  MAPK cascade signalling and synaptic plasticity , 2004, Nature Reviews Neuroscience.

[36]  H. R. Griffith,et al.  The Flexible Use of Multiple Cue Relationships in Spatial Navigation: A Comparison of Water Maze Performance Following Hippocampal, Medial Septal, Prefrontal Cortex, or Posterior Parietal Cortex Lesions , 1997, Neurobiology of Learning and Memory.

[37]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[38]  Gong-Wu Wang,et al.  Disconnection of the hippocampal–prefrontal cortical circuits impairs spatial working memory performance in rats , 2006, Behavioural Brain Research.

[39]  E. Kandel.  The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses , 2001, Science.

[40]  Yutaka Kirino,et al.  Time-Dependent Reorganization of the Brain Components Underlying Memory Retention in Trace Eyeblink Conditioning , 2003, The Journal of Neuroscience.

[41]  J. David Sweatt,et al.  The MAPK cascade is required for mammalian associative learning , 1998, Nature Neuroscience.

[42]  J. David Sweatt,et al.  A Requirement for the Mitogen-activated Protein Kinase Cascade in Hippocampal Long Term Potentiation* , 1997, The Journal of Biological Chemistry.

[43]  S. Peng,et al.  ERK in Learning and Memory: A Review of Recent Research , 2010, International journal of molecular sciences.

[44]  R. Sutherland,et al.  Complete or partial hippocampal damage produces equivalent retrograde amnesia for remote contextual fear memories , 2007, The European journal of neuroscience.

[45]  Larry R Squire,et al.  Medial Temporal Lobe Activity during Retrieval of Semantic Memory Is Related to the Age of the Memory , 2009, The Journal of Neuroscience.

[46]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .