Associative Memory Extinction Is Accompanied by Decayed Plasticity at Motor Cortical Neurons and Persistent Plasticity at Sensory Cortical Neurons

Associative memory is essential for cognition, in which associative memory cells and their plasticity presumably play important roles. The mechanism underlying associative memory extinction vs. maintenance remains unclear, which we have studied in a mouse model of cross-modal associative learning. Paired whisker and olfaction stimulations lead to a full establishment of odorant-induced whisker motion in training day 10, which almost disappears if paired stimulations are not given in a week, and then recovers after paired stimulation for an additional day. In mice that show associative memory, extinction and recovery, we have analyzed the dynamical plasticity of glutamatergic neurons in layers II–III of the barrel cortex and layers IV–V of the motor cortex. Compared with control mice, the rate of evoked spikes as well as the amplitude and frequency of excitatory postsynaptic currents increase, whereas the amplitude and frequency of inhibitory postsynaptic currents (IPSC) decrease at training day 10 in associative memory mice. Without paired training for a week, these plastic changes are persistent in the barrel cortex and decayed in the motor cortex. If paired training is given for an additional day to revoke associative memory, neuronal plasticity recovers in the motor cortex. Our study indicates persistent neuronal plasticity in the barrel cortex for cross-modal memory maintenance as well as the dynamical change of neuronal plasticity in the motor cortex for memory retrieval and extinction. In other words, the sensory cortices are essential for long-term memory while the behavior-related cortices with the inability of memory retrieval are correlated to memory extinction.

[1]  James M. Otis,et al.  Prefrontal cortex output circuits guide reward seeking through divergent cue encoding , 2017, Nature.

[2]  Michael Davis,et al.  Behavioral and Neural Analysis of Extinction , 2002, Neuron.

[3]  P. Dalby,et al.  Spontaneous changes , 2018, Oxford Scholarship Online.

[4]  V. Castellucci,et al.  Associative learning signals in the brain , 2008 .

[5]  Jin-Hui Wang,et al.  Associative memory cells: Formation, function and perspective , 2017, F1000Research.

[6]  Richard F. Thompson,et al.  Neural substrates of eyeblink conditioning: acquisition and retention. , 2003, Learning & memory.

[7]  O. Amaral,et al.  Memory labilization in reconsolidation and extinction – Evidence for a common plasticity system? , 2014, Journal of Physiology-Paris.

[8]  I. Bureau,et al.  Associative learning changes the organization of functional excitatory circuits targeting the supragranular layers of mouse barrel cortex , 2022 .

[9]  Wei Lu,et al.  Associations of Unilateral Whisker and Olfactory Signals Induce Synapse Formation and Memory Cell Recruitment in Bilateral Barrel Cortices: Cellular Mechanism for Unilateral Training Toward Bilateral Memory , 2016, Front. Cell. Neurosci..

[10]  Jin-Hui Wang,et al.  Glucocorticoid Induces Incoordination between Glutamatergic and GABAergic Neurons in the Amygdala , 2016, PloS one.

[11]  H. T. Blair,et al.  Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning. , 2001, Learning & memory.

[12]  R. R. Miller,et al.  What's elementary about associative learning? , 1997, Annual review of psychology.

[13]  R. C. Honey,et al.  Associative components of recognition memory , 2000, Current Opinion in Neurobiology.

[14]  Jin-Hui Wang,et al.  Incoordination among Subcellular Compartments Is Associated with Depression-Like Behavior Induced by Chronic Mild Stress , 2015, The international journal of neuropsychopharmacology.

[15]  Yasushi Miyashita,et al.  Forward Processing of Long-Term Associative Memory in Monkey Inferotemporal Cortex , 2003, The Journal of Neuroscience.

[16]  Jin-Hui Wang,et al.  Molecular Mechanism for Stress-Induced Depression Assessed by Sequencing miRNA and mRNA in Medial Prefrontal Cortex , 2016, PloS one.

[17]  Stephen Maren,et al.  Neural and cellular mechanisms of fear and extinction memory formation , 2012, Neuroscience & Biobehavioral Reviews.

[18]  Paul R. Benjamin,et al.  A Persistent Cellular Change in a Single Modulatory Neuron Contributes to Associative Long-Term Memory , 2003, Current Biology.

[19]  Jin-Hui Wang,et al.  Calcium‐calmodulin signalling pathway up‐regulates glutamatergic synaptic function in non‐pyramidal, fast spiking rat hippocampal CA1 neurons , 2001, The Journal of physiology.

[20]  I. Izquierdo,et al.  Retrieval and the Extinction of Memory , 2005, Cellular and Molecular Neurobiology.

[21]  Indre V. Viskontas,et al.  Advances in memory research: single-neuron recordings from the human medial temporal lobe aid our understanding of declarative memory , 2008, Current opinion in neurology.

[22]  Richard F. Thompson,et al.  Eye-blink conditioning is associated with changes in synaptic ultrastructure in the rabbit interpositus nuclei. , 2007, Learning & memory.

[23]  C. Borghi,et al.  Optimizing Lipid Pattern by Adding a Combined Nutraceutical or Pravastatin to Fenofibrate Treatment in Hypertriglyceridemic Subjects: Single Site, Randomized, Open-Label, Post-Market Clinical Investigation , 2018, High Blood Pressure & Cardiovascular Prevention.

[24]  J. Frey,et al.  'Synaptic tagging' and 'cross-tagging' and related associative reinforcement processes of functional plasticity as the cellular basis for memory formation. , 2008, Progress in brain research.

[25]  K. Deisseroth,et al.  Optogenetic stimulation of a hippocampal engram activates fear memory recall , 2012, Nature.

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

[27]  D. Paré,et al.  Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. , 2010, Physiological reviews.

[28]  Alcino J. Silva,et al.  A shared neural ensemble links distinct contextual memories encoded close in time , 2016, Nature.

[29]  P. Fitzgerald,et al.  Revisiting propranolol and PTSD: Memory erasure or extinction enhancement? , 2016, Neurobiology of Learning and Memory.

[30]  B. Ye,et al.  The Functional Upregulation of Piriform Cortex Is Associated with Cross-Modal Plasticity in Loss of Whisker Tactile Inputs , 2012, PloS one.

[31]  Wei Lu,et al.  Neurons in the barrel cortex turn into processing whisker and odor signals: a cellular mechanism for the storage and retrieval of associative signals , 2015, Front. Cell. Neurosci..

[32]  Na Chen,et al.  Upregulation of Glutamatergic Receptor-Channels is Associated with Cross-Modal Reflexes Encoded in Barrel Cortex and Piriform Cortex , 2014 .

[33]  Jin-Hui Wang,et al.  Voltage-independent sodium channels emerge for an expression of activity-induced spontaneous spikes in GABAergic neurons , 2014, Molecular Brain.

[34]  Yan Zhu,et al.  Upregulation of excitatory neurons and downregulation of inhibitory neurons in barrel cortex are associated with loss of whisker inputs , 2013, Molecular Brain.

[35]  K. Lattal,et al.  Epigenetics and persistent memory: implications for reconsolidation and silent extinction beyond the zero , 2013, Nature Neuroscience.

[36]  G. Feng,et al.  Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP , 2000, Neuron.

[37]  I. Mansuy,et al.  Epigenetics of memory and plasticity. , 2014, Progress in molecular biology and translational science.

[38]  Jianfeng Feng,et al.  Persistent Sodium Current Is a Nonsynaptic Substrate for Long-Term Associative Memory , 2008, Current Biology.

[39]  Alfredo Fontanini,et al.  Associative learning changes cross-modal representations in the gustatory cortex , 2016, eLife.

[40]  Wei Lu,et al.  Associative Memory Cells are Recruited to Encode Triple Sensory Signals via Synapse Formation , 2017 .

[41]  Kaoru Inokuchi,et al.  Overlapping memory trace indispensable for linking, but not recalling, individual memories , 2017, Science.

[42]  Charles D. Kopec,et al.  Experience-dependent modification of a central amygdala fear circuit , 2013, Nature Neuroscience.

[43]  Jin-Hui Wang.  Associative Memory Cells in Memory Trace , 2019, Associative Memory Cells: Basic Units of Memory Trace.

[44]  Wei Lu,et al.  Both Glutamatergic and Gabaergic Neurons are Recruited to be Associative Memory Cells , 2016 .

[45]  B. McNaughton,et al.  Spontaneous Changes of Neocortical Code for Associative Memory During Consolidation , 2008, Science.

[46]  Wei Xu,et al.  A Neural Circuit for Memory Specificity and Generalization , 2013, Science.

[47]  Corrado Bucherelli,et al.  Brain sites involved in fear memory reconsolidation and extinction of rodents , 2015, Neuroscience & Biobehavioral Reviews.

[48]  Jin-Hui Wang,et al.  Gain and fidelity of transmission patterns at cortical excitatory unitary synapses improve spike encoding , 2008, Journal of Cell Science.

[49]  J. David Sweatt,et al.  TET1 Controls CNS 5-Methylcytosine Hydroxylation, Active DNA Demethylation, Gene Transcription, and Memory Formation , 2013, Neuron.

[50]  Jin-Hui Wang,et al.  Physiological synaptic signals initiate sequential spikes at soma of cortical pyramidal neurons , 2011, Molecular Brain.

[51]  Yan Zhu,et al.  Sodium channel-mediated intrinsic mechanisms underlying the differences of spike programming among GABAergic neurons. , 2006, Biochemical and biophysical research communications.

[52]  Charles F. Stevens.  Presynaptic function , 2004, Current Opinion in Neurobiology.

[53]  Na Chen,et al.  Coordinated Plasticity between Barrel Cortical Glutamatergic and GABAergic Neurons during Associative Memory , 2016, Neural plasticity.

[54]  Mei Zhang,et al.  Calcium signal-dependent plasticity of neuronal excitability developed postnatally. , 2004, Journal of neurobiology.

[55]  Jin-Hui Wang,et al.  Homeostasis established by coordination of subcellular compartment plasticity improves spike encoding , 2008, Journal of Cell Science.

[56]  Jin-Hui Wang,et al.  Input-dependent subcellular localization of spike initiation between soma and axon at cortical pyramidal neurons , 2014, Molecular Brain.

[57]  Concha Bielza,et al.  New insights into the classification and nomenclature of cortical GABAergic interneurons , 2013, Nature Reviews Neuroscience.

[58]  Alexander E. Dityatev,et al.  Amygdala, Long-term Potentiation, and Fear Conditioning , 2005, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[59]  D. Molfese,et al.  Advancing Neuroscience Through Epigenetics: Molecular Mechanisms of Learning and Memory , 2011, Developmental neuropsychology.

[60]  Y. Zhu,et al.  Ca2+–calmodulin signalling pathway up-regulates GABA synaptic transmission through cytoskeleton-mediated mechanisms , 2004, Neuroscience.

[61]  Y. Humeau,et al.  Amygdala Inhibitory Circuits and the Control of Fear Memory , 2009, Neuron.

[62]  Jin-Hui Wang.  Short-term cerebral ischemia causes the dysfunction of interneurons and more excitation of pyramidal neurons in rats , 2003, Brain Research Bulletin.

[63]  W. Regehr,et al.  Short-term synaptic plasticity. , 2002, Annual review of physiology.

[64]  D. Knox.  The role of basal forebrain cholinergic neurons in fear and extinction memory , 2016, Neurobiology of Learning and Memory.

[65]  Eric R. Kandel,et al.  New mechanisms in memory storage: piRNAs and epigenetics , 2013, Trends in Neurosciences.

[66]  Yan Zhu,et al.  Upregulation of Barrel GABAergic Neurons Is Associated with Cross-Modal Plasticity in Olfactory Deficit , 2010, PloS one.

[67]  Min Sun,et al.  Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress , 2016, Translational psychiatry.

[68]  Na Chen,et al.  Afterhyperpolarization improves spike programming through lowering threshold potentials and refractory periods mediated by voltage-gated sodium channels. , 2006, Biochemical and biophysical research communications.

[69]  Andrew M. Poulos,et al.  The neuroscience of mammalian associative learning. , 2005, Annual review of psychology.

[70]  Fengyu Zhang,et al.  mGluR1,5 activation improves network asynchrony and GABAergic synapse attenuation in the amygdala: implication for anxiety-like behavior in DBA/2 mice , 2012, Molecular Brain.