Neural changes in Alzheimer’s disease from circuit to molecule: Perspective of optogenetics

Alzheimer's disease (AD), as a crucial neurodegenerative disorder, affects neural activities at many levels. Synaptic plasticity and neural circuits are most susceptible in AD, but the detailed mechanism is unclear. Optogenetic tools provide unprecedented spatio-temporal specificity to stimulate specific neural circuits or synaptic molecules to reveal the precise function of normal brain and mechanism of deficits in AD models. Furthermore, using optogenetics to stimulate neurons can rescue learning and memory loss caused by AD. It also has possibility to use light to control the Neurotransmitter receptors and their downstream signal pathway. These technical methods have broad therapeutic application prospect.

[1]  M. Moser,et al.  Impaired Spatial Representation in CA1 after Lesion of Direct Input from Entorhinal Cortex , 2008, Neuron.

[2]  P. Castillo,et al.  A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity. , 2015, Cell reports.

[3]  Xiu Song,et al.  Preferential enhancement of working memory in mice lacking adenosine A2A receptors , 2009, Brain Research.

[4]  L. Mucke,et al.  A network dysfunction perspective on neurodegenerative diseases , 2006, Nature.

[5]  J. Molgó,et al.  Early Presynaptic and Postsynaptic Calcium Signaling Abnormalities Mask Underlying Synaptic Depression in Presymptomatic Alzheimer's Disease Mice , 2012, The Journal of Neuroscience.

[6]  B R Rosen,et al.  Encoding novel face‐name associations: A functional MRI study , 2001, Human brain mapping.

[7]  I. Goshen.  The optogenetic revolution in memory research , 2014, Trends in Neurosciences.

[8]  E. Robinson,et al.  Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory , 2016, The Journal of Neuroscience.

[9]  George J. Augustine,et al.  Light-Emitting Channelrhodopsins for Combined Optogenetic and Chemical-Genetic Control of Neurons , 2013, PloS one.

[10]  S. Tomita,et al.  CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory , 2016, Neuron.

[11]  D. Salmon,et al.  Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment , 1991, Annals of neurology.

[12]  Jing Ren,et al.  Presynaptic Excitation via GABAB Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression , 2016, Cell.

[13]  C. Garner,et al.  Presynaptic function in health and disease , 2011, Trends in Neurosciences.

[14]  L. Fratiglioni,et al.  Interactive effects of KIBRA and CLSTN2 polymorphisms on episodic memory in old-age unipolar depression , 2014, Neuropsychologia.

[15]  G. Sancesario,et al.  Amyloid β, Glutamate, Excitotoxicity in Alzheimer's Disease: Are We on the Right Track? , 2013, CNS neuroscience & therapeutics.

[16]  C. Parsons,et al.  Alzheimer's disease, β‐amyloid, glutamate, NMDA receptors and memantine – searching for the connections , 2012, British journal of pharmacology.

[17]  Stefano Fusi,et al.  Hippocampal-prefrontal input supports spatial encoding in working memory , 2015, Nature.

[18]  G. Halliday,et al.  Aβ-dependent reduction of NCAM2-mediated synaptic adhesion contributes to synapse loss in Alzheimer's disease , 2015, Nature Communications.

[19]  Ping-Li Ma,et al.  Age-dependent alterations in the presynaptic active zone in a Drosophila model of Alzheimer's Disease , 2013, Neurobiology of Disease.

[20]  Pere Garriga,et al.  Light-driven activation of beta 2-adrenergic receptor signaling by a chimeric rhodopsin containing the beta 2-adrenergic receptor cytoplasmic loops. , 2005, Biochemistry.

[21]  Shinya Kuroda,et al.  An optogenetic system for interrogating the temporal dynamics of Akt , 2015, Scientific Reports.

[22]  R. Anwyl,et al.  Glun2b Subunit-containing Nmda Receptor Antagonists Prevent A␤-mediated Synaptic Plasticity Disruption in Vivo Abrogation of A␤-mediated Disruption of Hippocampal Synaptic Plasticity in Vivo by Antagonists Selective for Glun2b-containing , 2022 .

[23]  Lars-Oliver Essen,et al.  A LOV2 domain-based optogenetic tool to control protein degradation and cellular function. , 2013, Chemistry & biology.

[24]  J. David Sweatt,et al.  β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In Vitro and In Vivo Mechanisms Related to Alzheimer's Disease , 2001, The Journal of Neuroscience.

[25]  Thomas J. Jentsch,et al.  Optogenetic Acidification of Synaptic Vesicles and Lysosomes , 2015, Nature Neuroscience.

[26]  J. Vickers,et al.  Altered synapses and gliotransmission in Alzheimer's disease and AD model mice , 2013, Neurobiology of Aging.

[27]  Attila Losonczy,et al.  Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition , 2016, Science.

[28]  J. Feldon,et al.  Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning. , 2011, Learning & memory.

[29]  W. K. Cullen,et al.  Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo , 2002, Nature.

[30]  Qiang Zhou,et al.  NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease , 2013, Nature Reviews Neuroscience.

[31]  A. Palmeri,et al.  Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory , 2016, Scientific Reports.

[32]  G. Šimić,et al.  Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease , 1997, The Journal of comparative neurology.

[33]  Sylvain Williams,et al.  Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms , 2016, The Journal of Neuroscience.

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

[35]  Tomonori Takeuchi,et al.  The synaptic plasticity and memory hypothesis: encoding, storage and persistence , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[36]  Z. Josh Huang,et al.  A Cortico-Hippocampal Learning Rule Shapes Inhibitory Microcircuit Activity to Enhance Hippocampal Information Flow , 2013, Neuron.

[37]  David A. Drachman,et al.  Synaptic loss in Alzheimer's disease and other dementias , 1989, Neurology.

[38]  K. Deisseroth,et al.  Dynamics of Retrieval Strategies for Remote Memories , 2011, Cell.

[39]  Kelly O'Keefe,et al.  Hippocampal Hyperactivation Associated with Cortical Thinning in Alzheimer's Disease Signature Regions in Non-Demented Elderly Adults , 2011, The Journal of Neuroscience.

[40]  T. Abel,et al.  Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. , 2001, Learning & memory.

[41]  Thomas M. Sanderson,et al.  Hippocampal metabotropic glutamate receptor long‐term depression in health and disease: focus on mitogen‐activated protein kinase pathways , 2016, Journal of neurochemistry.

[42]  Awanish Kumar,et al.  Current and novel therapeutic molecules and targets in Alzheimer's disease. , 2016, Journal of the Formosan Medical Association = Taiwan yi zhi.

[43]  M. Van der Linden,et al.  Apathy and Executive Dysfunction in Alzheimer Disease , 2010, Alzheimer disease and associated disorders.

[44]  Raag D. Airan,et al.  Temporally precise in vivo control of intracellular signalling , 2009, Nature.

[45]  S. Raghavachari,et al.  Mechanisms of CaMKII action in long-term potentiation , 2012, Nature Reviews Neuroscience.

[46]  Qi Ding,et al.  Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation , 2016, Learning & memory.

[47]  K. Giese,et al.  The roles of protein kinases in learning and memory. , 2013, Learning & memory.

[48]  R. Murray,et al.  Erratum: Reciprocal causation models of cognitive vs volumetric cerebral intermediate phenotypes for schizophrenia in a pan-European twin cohort , 2015, Molecular Psychiatry.

[49]  S. Samarasinghe,et al.  Modelling the dynamics of CaMKII-NMDAR complex related to memory formation in synapses: the possible roles of threonine 286 autophosphorylation of CaMKII in long term potentiation. , 2015, Journal of theoretical biology.

[50]  Attila Losonczy,et al.  Dendritic Inhibition in the Hippocampus Supports Fear Learning , 2014, Science.

[51]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[52]  Michele Pignatelli,et al.  Engram cells retain memory under retrograde amnesia , 2015, Science.

[53]  Li-Huei Tsai,et al.  Early remodeling of the neocortex upon episodic memory encoding , 2014, Proceedings of the National Academy of Sciences.

[54]  Michael Z. Lin,et al.  Characterization of engineered channelrhodopsin variants with improved properties and kinetics. , 2009, Biophysical journal.

[55]  Clifford R. Jack,et al.  Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer’s Association Research Roundtable Workgroup , 2011, Alzheimer's & Dementia.

[56]  F. Schmitt,et al.  Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment , 2006, Neurobiology of Aging.

[57]  Z. Gu,et al.  Timing-Dependent Septal Cholinergic Induction of Dynamic Hippocampal Synaptic Plasticity , 2011, Neuron.

[58]  Edith Lesburguères,et al.  Early Tagging of Cortical Networks Is Required for the Formation of Enduring Associative Memory , 2011, Science.

[59]  T. H. Ferreira-Vieira,et al.  Alzheimer's Disease: Targeting the Cholinergic System , 2016, Current neuropharmacology.

[60]  W. M. van der Flier,et al.  Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease. , 2015, JAMA neurology.

[61]  S. A. Hussaini,et al.  Neuronal activity enhances tau propagation and tau pathology in vivo , 2016, Nature Neuroscience.

[62]  R. Mayeux,et al.  Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease , 2013, Nature Neuroscience.

[63]  O. Yizhar,et al.  Biophysical constraints of optogenetic inhibition at presynaptic terminals , 2016, Nature Neuroscience.

[64]  M. Whittington,et al.  Long-Range–Projecting GABAergic Neurons Modulate Inhibition in Hippocampus and Entorhinal Cortex , 2012, Science.

[65]  Michael Z. Lin,et al.  Optical control of cell signaling by single-chain photoswitchable kinases , 2017, Science.

[66]  J. Wu,et al.  A novel mechanism of memory loss in Alzheimer’s disease mice via the degeneration of entorhinal–CA1 synapses , 2016, Molecular Psychiatry.

[67]  Lacey J. Kitch,et al.  Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory , 2015, Neuron.

[68]  Matias D Zurbriggen,et al.  Red Light-Regulated Reversible Nuclear Localization of Proteins in Mammalian Cells and Zebrafish. , 2015, ACS synthetic biology.

[69]  K. Giese,et al.  Calcium/calmodulin-dependent kinase II and Alzheimer’s disease , 2015, Molecular Brain.

[70]  Sadegh Nabavi,et al.  Optogenetic Inhibition of Synaptic Release with Chromophore-Assisted Light Inactivation (CALI) , 2013, Neuron.

[71]  Shaomin Li,et al.  Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory , 2008, Nature Medicine.

[72]  G. Quirk,et al.  Revisiting the Role of Infralimbic Cortex in Fear Extinction with Optogenetics , 2015, The Journal of Neuroscience.

[73]  B. McNaughton,et al.  Declarative memory consolidation in humans: a prospective functional magnetic resonance imaging study. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[74]  William J. Ray,et al.  A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain , 1999, Nature.

[75]  Christina L. Ruby,et al.  Adenosine Transporter ENT1 Regulates the Acquisition of Goal-Directed Behavior and Ethanol Drinking through A2A Receptor in the Dorsomedial Striatum , 2013, The Journal of Neuroscience.

[76]  R. Huganir,et al.  Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and Promotes Tauopathy-Related Memory Loss , 2016, Neuron.

[77]  Sachin S. Deshmukh,et al.  Functional correlates of the lateral and medial entorhinal cortex: objects, path integration and local–global reference frames , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[78]  Alexander J. Rivest,et al.  Entorhinal Cortex Layer III Input to the Hippocampus Is Crucial for Temporal Association Memory , 2011, Science.

[79]  Hyejin Kang,et al.  Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory , 2004, Cell.

[80]  D. Selkoe,et al.  Amyloid β-peptide is produced by cultured cells during normal metabolism , 1992, Nature.

[81]  K. Deisseroth,et al.  Optogenetic investigation of neural circuits underlying brain disease in animal models , 2012, Nature Reviews Neuroscience.

[82]  D. Selkoe.  Alzheimer's Disease Is a Synaptic Failure , 2002, Science.

[83]  Dheeraj S. Roy,et al.  Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease , 2016, Nature.

[84]  L. Aguayo,et al.  The Level of NMDA Receptor in the Membrane Modulates Amyloid-β Association and Perforation. , 2016, Journal of Alzheimer's disease : JAD.

[85]  G. Martin,et al.  The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens , 2015, Front. Synaptic Neurosci..

[86]  B. Hyman,et al.  Neuropathological alterations in Alzheimer disease. , 2011, Cold Spring Harbor perspectives in medicine.

[87]  R. Colbran,et al.  CaMKII: a molecular substrate for synaptic plasticity and memory. , 2014, Progress in molecular biology and translational science.

[88]  Kelly R. Tan,et al.  Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning , 2012, Nature.

[89]  X. Wang,et al.  Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling , 2016, Proceedings of the National Academy of Sciences.

[90]  K. Deisseroth,et al.  Ultrafast optogenetic control , 2010, Nature Neuroscience.

[91]  C. Davis,et al.  Obesity Elicits Interleukin 1-Mediated Deficits in Hippocampal Synaptic Plasticity , 2014, The Journal of Neuroscience.

[92]  George J Augustine,et al.  Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation , 2016, Proceedings of the National Academy of Sciences.

[93]  R. Brett,et al.  Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Impairs Synaptic Plasticity and Hippocampal-Dependent Memory , 2016, The Journal of Neuroscience.

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

[95]  Sabina Sonia Tangaro,et al.  Integrating longitudinal information in hippocampal volume measurements for the early detection of Alzheimer's disease , 2016, NeuroImage.

[96]  K. Deisseroth,et al.  Synaptic Encoding of Fear Extinction in mPFC-amygdala Circuits , 2013, Neuron.

[97]  Y. Iino,et al.  Optogenetic activation of axon guidance receptors controls direction of neurite outgrowth , 2016, Scientific Reports.

[98]  Iryna Leshchyns’ka,et al.  Synaptic Cell Adhesion Molecules in Alzheimer's Disease , 2016, Neural plasticity.

[99]  G. Barker,et al.  Object-in-Place Associative Recognition Memory Depends on Glutamate Receptor Neurotransmission Within Two Defined Hippocampal-Cortical Circuits: A Critical Role for AMPA and NMDA Receptors in the Hippocampus, Perirhinal, and Prefrontal Cortices , 2013, Cerebral cortex.

[100]  Lief E. Fenno,et al.  Neocortical excitation/inhibition balance in information processing and social dysfunction , 2011, Nature.

[101]  J. Coyle,et al.  Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis , 1981, Annals of neurology.

[102]  Lukas C. Kapitein,et al.  Optogenetic control of organelle transport and positioning , 2015, Nature.

[103]  Weikun Guo,et al.  Astrocytic adenosine receptor A2A and Gs-coupled signaling regulate memory , 2014, Nature Neuroscience.

[104]  R. Mahley,et al.  GABAergic interneuron dysfunction impairs hippocampal neurogenesis in adult apolipoprotein E4 knockin mice. , 2009, Cell stem cell.

[105]  Lief E. Fenno,et al.  Chronic optogenetic activation augments Aβ pathology in a mouse model of Alzheimer disease , 2022 .

[106]  M. Corbetta,et al.  Common Blood Flow Changes across Visual Tasks: II. Decreases in Cerebral Cortex , 1997, Journal of Cognitive Neuroscience.

[107]  L. Mucke,et al.  Alzheimer Mechanisms and Therapeutic Strategies , 2012, Cell.

[108]  E. Boyden,et al.  Gamma frequency entrainment attenuates amyloid load and modifies microglia , 2016, Nature.

[109]  Wade G. Regehr,et al.  Achieving High-Frequency Optical Control of Synaptic Transmission , 2014, The Journal of Neuroscience.

[110]  Ben A. Barres,et al.  Complement and microglia mediate early synapse loss in Alzheimer mouse models , 2016, Science.

[111]  B. Kuhlman,et al.  A genetically-encoded photoactivatable Rac controls the motility of living cells , 2009, Nature.

[112]  J. Lisman,et al.  The molecular basis of CaMKII function in synaptic and behavioural memory , 2002, Nature Reviews Neuroscience.

[113]  A. Frick,et al.  Early synaptic deficits in the APP/PS1 mouse model of Alzheimer's disease involve neuronal adenosine A2A receptors , 2016, Nature Communications.

[114]  S. Tonegawa,et al.  Island Cells Control Temporal Association Memory , 2014, Science.

[115]  K. Deisseroth.  Optogenetics: 10 years of microbial opsins in neuroscience , 2015, Nature Neuroscience.

[116]  J. Ziburkus,et al.  Inhibitory Neuron and Hippocampal Circuit Dysfunction in an Aged Mouse Model of Alzheimer's Disease , 2013, PloS one.

[117]  L. Mucke,et al.  Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks , 2010, Nature Neuroscience.

[118]  Conor Liston,et al.  Projections from neocortex mediate top-down control of memory retrieval , 2015, Nature.

[119]  Michael Z. Lin,et al.  Optical Control of Protein Activity by Fluorescent Protein Domains , 2012, Science.