Skip to main content
SpringerLink
Log in

Investigating learning-related neural circuitry with chronic in vivo optical imaging

  • Review
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

Fundamental aspects of brain function, including development, plasticity, learning, and memory, can take place over time scales of days to years. Chronic in vivo imaging of neural activity with cellular resolution is a powerful method for tracking the long-term activity of neural circuits. We review recent advances in our understanding of neural circuit function from diverse brain regions that have been enabled by chronic in vivo cellular imaging. Insight into the neural basis of learning and decision-making, in particular, benefit from the ability to acquire longitudinal data from genetically identified neuronal populations, deep brain areas, and subcellular structures. We propose that combining chronic imaging with further experimental and computational innovations will advance our understanding of the neural circuit mechanisms of brain function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

a Adapted from Margolis et al. (2012), b Adapted from Kim et al. (2016), c Adapted from Bocarsly et al. (2015), Adapted from Andermann et al. (2013)

Fig. 2

a–c Adapted from Katlowitz et al. (2018), d–e Adapted from Hainmueller and Bartos (2018)

Fig. 3

a Adapted from Chen et al. (2015a), b Adapted from Poort et al. (2015), c Adapted from Grewe et al. (2017)

Similar content being viewed by others

References

  • Akassoglou K, Merlini M, Rafalski VA et al (2017) Imaging of CNS injury and disease. J Neurosci Off J Soc Neurosci 37:10808–10816

    CAS  Google Scholar 

  • Alivisatos AP, Chun M, Church GM et al (2015) A national network of neurotechnology centers for the BRAIN initiative. Neuron 88:445–448

    CAS  PubMed  PubMed Central  Google Scholar 

  • Andermann ML, Gilfoy NB, Goldey GJ et al (2013) Chronic cellular imaging of entire cortical columns in awake mice using microprisms. Neuron 80:900–913

    CAS  PubMed  Google Scholar 

  • Bando Y, Sakamoto M, Kim S et al (2019) Comparative evaluation of genetically encoded voltage indicators. Cell reports 26:802–813.e4

    CAS  PubMed  Google Scholar 

  • Barretto RPJ, Messerschmidt B, Schnitzer MJ (2009) In vivo fluorescence imaging with high-resolution microlenses. Nat Methods 6:511–512

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barth AL, Poulet JFA (2012) Experimental evidence for sparse firing in the neocortex. Trends Neurosci 35:345–355

    CAS  PubMed  Google Scholar 

  • Bassett DS, Sporns O (2017) Network neuroscience. Nat Neurosci 20:353–364

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bedbrook CN, Deverman BE, Gradinaru V (2018) Viral strategies for targeting the central and peripheral nervous systems. Annu Rev Neurosci 41:323–348

    CAS  PubMed  Google Scholar 

  • Berens P, Freeman J, Deneux T et al (2018) Community-based benchmarking improves spike rate inference from two-photon calcium imaging data. PLoS Comput Biol 14:e1006157

    PubMed  PubMed Central  Google Scholar 

  • Berry KP, Nedivi E (2017) Spine dynamics: are they all the same? Neuron 96:43–55

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bloem B, Huda R, Sur M, Graybiel AM (2017) Two-photon imaging in mice shows striosomes and matrix have overlapping but differential reinforcement-related responses. Elife 6:e32353

    PubMed  PubMed Central  Google Scholar 

  • Bocarsly ME, Jiang W-C, Wang C et al (2015) Minimally invasive microendoscopy system for in vivo functional imaging of deep nuclei in the mouse brain. Biomed Opt Express 6:4546–4556

    PubMed  PubMed Central  Google Scholar 

  • Bootman MD, Allman S, Rietdorf K, Bultynck G (2018) Deleterious effects of calcium indicators within cells; an inconvenient truth. Cell Calcium 73:82–87

    CAS  PubMed  Google Scholar 

  • Broussard GJ, Liang Y, Fridman M et al (2018) In vivo measurement of afferent activity with axon-specific calcium imaging. Nat Neurosci 21:1272–1280

    CAS  PubMed  PubMed Central  Google Scholar 

  • Burgess CR, Ramesh RN, Sugden AU et al (2016) Hunger-dependent enhancement of food cue responses in mouse postrhinal cortex and lateral amygdala. Neuron 91:1154–1169

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cai DJ, Aharoni D, Shuman T et al (2016) A shared neural ensemble links distinct contextual memories encoded close in time. Nature 534:115–118

    CAS  PubMed  PubMed Central  Google Scholar 

  • Carrillo-Reid L, Han S, Yang W et al (2019) Controlling visually guided behavior by holographic recalling of cortical ensembles. Cell 178:447–457.e5

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chatterjee S, Sullivan HA, MacLennan BJ et al (2018) Nontoxic, double-deletion-mutant rabies viral vectors for retrograde targeting of projection neurons. Nat Neurosci 21:638–646

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen JL, Nedivi E (2010) Neuronal structural remodeling: is it all about access? Curr Opin Neurobiol 20:557–562

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen JL, Carta S, Soldado-Magraner J et al (2013a) Behaviour-dependent recruitment of long-range projection neurons in somatosensory cortex. Nature 499:336–340

    CAS  PubMed  Google Scholar 

  • Chen T-W, Wardill TJ, Sun Y et al (2013b) Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499:295–300

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen JL, Margolis DJ, Stankov A et al (2015a) Pathway-specific reorganization of projection neurons in somatosensory cortex during learning. Nat Neurosci 18:1101–1108

    PubMed  Google Scholar 

  • Chen SX, Kim AN, Peters AJ, Komiyama T (2015b) Subtype-specific plasticity of inhibitory circuits in motor cortex during motor learning. Nat Neurosci 18:1109–1115

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen JL, Voigt FF, Javadzadeh M et al (2016) Long-range population dynamics of anatomically defined neocortical networks. Elife 5:e14679

    PubMed  PubMed Central  Google Scholar 

  • Clopath C, Bonhoeffer T, Hübener M, Rose T (2017) Variance and invariance of neuronal long-term representations. Philos Trans R Soc B Biol Sci 372:20160161

    Google Scholar 

  • Crochet S, Lee S-H, Petersen CCH (2018) Neural circuits for goal-directed sensorimotor transformations. Trends Neurosci 42:66–77

    PubMed  Google Scholar 

  • Crowe SE, Ellis-Davies GCR (2014) Longitudinal in vivo two-photon fluorescence imaging. J Comp Neurol 522:1708–1727

    PubMed  PubMed Central  Google Scholar 

  • Daigle TL, Madisen L, Hage TA et al (2018) A suite of transgenic driver and reporter mouse lines with enhanced brain-cell-type targeting and functionality. Cell 174:465–480.e22

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dana H, Chen T-W, Hu A et al (2014) Thy1-GCaMP6 transgenic mice for neuronal population imaging in vivo. PLoS ONE 9:e108697

    PubMed  PubMed Central  Google Scholar 

  • Dana H, Mohar B, Sun Y et al (2016) Sensitive red protein calcium indicators for imaging neural activity. Elife 5:e12727

    PubMed  PubMed Central  Google Scholar 

  • Dana H, Novak O, Guardado-Montesino M et al (2018) Thy1 transgenic mice expressing the red fluorescent calcium indicator jRGECO1a for neuronal population imaging in vivo. PLoS One 13:e0205444

    PubMed  PubMed Central  Google Scholar 

  • Dana H, Sun Y, Mohar B et al (2019) High-performance calcium sensors for imaging activity in neuronal populations and microcompartments. Nat Methods 16:649–657

    CAS  PubMed  Google Scholar 

  • Deisseroth K (2015) Optogenetics: 10 years of microbial opsins in neuroscience. Nat Neurosci 18:1213–1225

    CAS  PubMed  PubMed Central  Google Scholar 

  • Denk W, Svoboda K (1997) Photon upmanship: why multiphoton imaging is more than a gimmick. Neuron 18:351–357

    CAS  PubMed  Google Scholar 

  • Dhawale AK, Poddar R, Wolff SB et al (2017) Automated long-term recording and analysis of neural activity in behaving animals. Elife 6:e27702

    PubMed  PubMed Central  Google Scholar 

  • Dombeck D, Tank D (2014) Two-photon imaging of neural activity in awake mobile mice. Cold Spring Harb Protoc 2014:726–736

    PubMed  Google Scholar 

  • Dombeck DA, Harvey CD, Tian L et al (2010) Functional imaging of hippocampal place cells at cellular resolution during virtual navigation. Nat Neurosci 13:1433–1440

    CAS  PubMed  PubMed Central  Google Scholar 

  • Driscoll LN, Pettit NL, Minderer M et al (2017) Dynamic reorganization of neuronal activity patterns in parietal cortex. Cell 170:986–999.e16

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eyo UB, Mo M, Yi M-H et al (2018) P2Y12R-dependent translocation mechanisms gate the changing microglial landscape. Cell Rep 23:959–966

    CAS  PubMed  PubMed Central  Google Scholar 

  • Feng J, Zhang C, Lischinsky JE et al (2019) A genetically encoded fluorescent sensor for rapid and specific in vivo detection of norepinephrine. Neuron 102:745–761.e8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Flusberg BA, Nimmerjahn A, Cocker ED et al (2008) High-speed, miniaturized fluorescence microscopy in freely moving mice. Nat Methods 5:935–938

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frank AC, Huang S, Zhou M et al (2018) Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory. Nat Commun 9:422

    PubMed  PubMed Central  Google Scholar 

  • Fu M, Yu X, Lu J, Zuo Y (2012) Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo. Nature 483:92–95

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fu T-M, Hong G, Zhou T et al (2016) Stable long-term chronic brain mapping at the single-neuron level. Nat Methods 13:875–882

    CAS  PubMed  Google Scholar 

  • Gauthier JL, Tank DW (2018) A dedicated population for reward coding in the hippocampus. Neuron 99:179–193.e7

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gdalyahu A, Tring E, Polack P-O et al (2012) Associative fear learning enhances sparse network coding in primary sensory cortex. Neuron 75:121–132

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ghanbari L, Carter RE, Rynes ML et al (2019) Cortex-wide neural interfacing via transparent polymer skulls. Nat Commun 10:1500

    PubMed  PubMed Central  Google Scholar 

  • Giovannucci A, Friedrich J, Gunn P et al (2019) CaImAn an open source tool for scalable calcium imaging data analysis. Elife 8:e38173

    PubMed  PubMed Central  Google Scholar 

  • Glausier JR, Lewis DA (2013) Dendritic spine pathology in schizophrenia. Neuroscience 251:90–107

    CAS  PubMed  Google Scholar 

  • Glickfeld LL, Andermann ML, Bonin V, Reid RC (2013) Cortico-cortical projections in mouse visual cortex are functionally target specific. Nat Neurosci 16:219–226

    CAS  PubMed  Google Scholar 

  • Goldey GJ, Roumis DK, Glickfeld LL et al (2014) Removable cranial windows for long-term imaging in awake mice. Nat Protoc 9:2515–2538

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gong Y, Huang C, Li JZ et al (2015) High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor. Science 350:1361–1366

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grewe BF, Gründemann J, Kitch LJ et al (2017) Neural ensemble dynamics underlying a long-term associative memory. Nature 543:670–675

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grienberger C, Konnerth A (2012) Imaging calcium in neurons. Neuron 73:862–885

    CAS  PubMed  Google Scholar 

  • Grutzendler J, Kasthuri N, Gan W-B (2002) Long-term dendritic spine stability in the adult cortex. Nature 420:812–816

    CAS  PubMed  Google Scholar 

  • Guo ZV, Li N, Huber D et al (2014) Flow of cortical activity underlying a tactile decision in mice. Neuron 81:179–194

    CAS  PubMed  Google Scholar 

  • Hainmueller T, Bartos M (2018) Parallel emergence of stable and dynamic memory engrams in the hippocampus. Nature 558:292–296

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hamel EJO, Grewe BF, Parker JG, Schnitzer MJ (2015) Cellular level brain imaging in behaving mammals: an engineering approach. Neuron 86:140–159

    CAS  PubMed  PubMed Central  Google Scholar 

  • Helmchen F, Denk W (2005) Deep tissue two-photon microscopy. Nat methods 2:932–940

    CAS  PubMed  Google Scholar 

  • Hill RA, Damisah EC, Chen F et al (2017) Targeted two-photon chemical apoptotic ablation of defined cell types in vivo. Nat Commun 8:15837

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hill RA, Li AM, Grutzendler J (2018) Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nat Neurosci 21:683–695

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hires SA, Tian L, Looger LL (2008) Reporting neural activity with genetically encoded calcium indicators. Brain Cell Biol 36:69–86

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hochbaum DR, Zhao Y, Farhi SL et al (2014) All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat Methods 11:825–833

    CAS  PubMed  PubMed Central  Google Scholar 

  • Holtmaat A, Svoboda K (2009) Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev Neurosci 10:647–658

    CAS  PubMed  Google Scholar 

  • Holtmaat A, Wilbrecht L, Knott GW et al (2006) Experience-dependent and cell-type-specific spine growth in the neocortex. Nature 441:979–983

    CAS  PubMed  Google Scholar 

  • Huang C, Maxey JR, Sinha S et al (2018) Long-term optical brain imaging in live adult fruit flies. Nat Commun 9:872

    PubMed  PubMed Central  Google Scholar 

  • Huber D, Gutnisky DA, Peron S et al (2012) Multiple dynamic representations in the motor cortex during sensorimotor learning. Nature 484:473–478

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hui GK, Wong KL, Chavez CM et al (2009) Conditioned tone control of brain reward behavior produces highly specific representational gain in the primary auditory cortex. Neurobiol Learn Mem 92:27–34

    PubMed  PubMed Central  Google Scholar 

  • Jacob AD, Ramsaran AI, Mocle AJ et al (2018) A compact head-mounted endoscope for in vivo calcium imaging in freely behaving mice. Curr Protoc Neurosci 84:e51

    PubMed  Google Scholar 

  • Jing M, Zhang P, Wang G et al (2018) A genetically encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nat Biotechnol 36:726–737

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jonckers E, Shah D, Hamaide J et al (2015) The power of using functional fMRI on small rodents to study brain pharmacology and disease. Front Pharmacol 6:231

    PubMed  PubMed Central  Google Scholar 

  • Jorgenson LA, Newsome WT, Anderson DJ et al (2015) The BRAIN Initiative: developing technology to catalyse neuroscience discovery. Philos Trans R Soc B Biol Sci 370:20140164

    Google Scholar 

  • Jung JC, Mehta AD, Aksay E et al (2004) In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy. J Neurophysiol 92:3121–3133

    PubMed  Google Scholar 

  • Katlowitz KA, Picardo MA, Long MA (2018) Stable sequential activity underlying the maintenance of a precisely executed skilled behavior. Neuron 98:1133–1140.e3

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kato HK, Chu MW, Isaacson JS, Komiyama T (2012) Dynamic sensory representations in the olfactory bulb: modulation by wakefulness and experience. Neuron 76:962–975

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kerr JND, Denk W (2008) Imaging in vivo: watching the brain in action. Nat Rev Neurosci 9:195–205

    CAS  PubMed  Google Scholar 

  • Khambhati AN, Sizemore AE, Betzel RF, Bassett DS (2018) Modeling and interpreting mesoscale network dynamics. NeuroImage 180:337–349

    PubMed  Google Scholar 

  • Kim TH, Zhang Y, Lecoq J et al (2016) Long-term optical access to an estimated one million neurons in the live mouse cortex. Cell reports 17:3385–3394

    CAS  PubMed  Google Scholar 

  • Knobloch M, Mansuy IM (2008) Dendritic spine loss and synaptic alterations in Alzheimer’s disease. Mol Neurobiol 37:73–82

    CAS  PubMed  Google Scholar 

  • Knöpfel T, Tomita K, Shimazaki R, Sakai R (2003) Optical recordings of membrane potential using genetically targeted voltage-sensitive fluorescent proteins. Methods 30:42–48

    PubMed  Google Scholar 

  • Kolasinski J, Makin TR, Jbabdi S et al (2016) Investigating the stability of fine-grain digit somatotopy in individual human participants. J Neurosci Off J Soc Neurosci 36:1113–1127

    CAS  Google Scholar 

  • Komiyama T, Sato TR, O’Connor DH et al (2010) Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice. Nature 464:1182–1186

    CAS  PubMed  Google Scholar 

  • Kuhlman SJ, O’Connor DH, Fox K, Svoboda K (2014) Structural plasticity within the barrel cortex during initial phases of whisker-dependent learning. J Neurosci Off J Soc Neurosci 34:6078–6083

    CAS  Google Scholar 

  • Kupferschmidt DA, Juczewski K, Cui G et al (2017) Parallel, but dissociable, processing in discrete corticostriatal inputs encodes skill learning. Neuron 96:476–489.e5

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lacasa L, Luque B, Ballesteros F et al (2008) From time series to complex networks: the visibility graph. Proc Natl Acad Sci United States Am 105:4972–4975

    CAS  Google Scholar 

  • Lacefield CO, Pnevmatikakis EA, Paninski L, Bruno RM (2019) Reinforcement learning recruits somata and apical dendrites across layers of primary sensory cortex. Cell reports 26:2000–2008.e2

    CAS  PubMed  Google Scholar 

  • Lai CSW, Franke TF, Gan W-B (2012) Opposite effects of fear conditioning and extinction on dendritic spine remodelling. Nature 483:87–91

    CAS  PubMed  Google Scholar 

  • Lai CSW, Adler A, Gan W-B (2018) Fear extinction reverses dendritic spine formation induced by fear conditioning in the mouse auditory cortex. Proc Natl Acad Sci USA 115:9306–9311

    PubMed  PubMed Central  Google Scholar 

  • Le Merre P, Esmaeili V, Charrière E et al (2018) Reward-based learning drives rapid sensory signals in medial prefrontal cortex and dorsal hippocampus necessary for goal-directed behavior. Neuron 97:83–91.e5

    PubMed  PubMed Central  Google Scholar 

  • Lecoq J, Savall J, Vučinić D et al (2014) Visualizing mammalian brain area interactions by dual-axis two-photon calcium imaging. Nat Neurosci 17:1825–1829

    CAS  PubMed  PubMed Central  Google Scholar 

  • LeMessurier AM, Feldman DE (2018) Plasticity of population coding in primary sensory cortex. Curr Opin Neurobiol 53:50–56

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lin MZ, Schnitzer MJ (2016) Genetically encoded indicators of neuronal activity. Nat Neurosci 19:1142–1153

    PubMed  PubMed Central  Google Scholar 

  • Livneh Y, Ramesh RN, Burgess CR et al (2017) Homeostatic circuits selectively gate food cue responses in insular cortex. Nature 546:611–616

    CAS  PubMed  PubMed Central  Google Scholar 

  • Low RJ, Gu Y, Tank DW (2014) Cellular resolution optical access to brain regions in fissures: imaging medial prefrontal cortex and grid cells in entorhinal cortex. Proc Natl Acad Sci USA 111:18739–18744

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lu R, Sun W, Liang Y et al (2017) Video-rate volumetric functional imaging of the brain at synaptic resolution. Nat Neurosci 20:620–628

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lütcke H, Margolis DJ, Helmchen F (2013) Steady or changing? Long-term monitoring of neuronal population activity. Trends Neurosci 36:375–384

    PubMed  Google Scholar 

  • Madisen L, Garner AR, Shimaoka D et al (2015) Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance. Neuron 85:942–958

    CAS  PubMed  PubMed Central  Google Scholar 

  • Makino H, Hwang EJ, Hedrick NG, Komiyama T (2016) Circuit mechanisms of sensorimotor learning. Neuron 92:705–721

    CAS  PubMed  PubMed Central  Google Scholar 

  • Makino H, Ren C, Liu H et al (2017) Transformation of cortex-wide emergent properties during motor learning. Neuron 94:880–890.e8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mank M, Santos AF, Direnberger S et al (2008) A genetically encoded calcium indicator for chronic in vivo two-photon imaging. Nat Methods 5:805–811

    CAS  PubMed  Google Scholar 

  • Margolis DJ, Lütcke H, Helmchen F et al (2011) Chronic two-photon imaging of neural activity in the anesthetized and awake behaving rodent. Optical imaging of neocortical dynamics. Humana Press, Totowa, pp 151–173

    Google Scholar 

  • Margolis DJ, Lütcke H, Schulz K et al (2012) Reorganization of cortical population activity imaged throughout long-term sensory deprivation. Nat Neurosci 15:1539–1546

    CAS  PubMed  Google Scholar 

  • Margolis DJ, Lütcke H, Helmchen F (2014) Microcircuit dynamics of map plasticity in barrel cortex. Curr Opin Neurobiol 24:76–81

    CAS  PubMed  Google Scholar 

  • Marshel JH, Kim YS, Machado TA et al (2019) Cortical layer-specific critical dynamics triggering perception. Science 365:eaaw5202

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martínez-Cerdeño V (2017) Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models. Dev Neurobiol 77:393–404

    PubMed  Google Scholar 

  • Marvin JS, Borghuis BG, Tian L et al (2013) An optimized fluorescent probe for visualizing glutamate neurotransmission. Nat Methods 10:162–170

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marvin JS, Shimoda Y, Magloire V, et al (2019) A genetically encoded fluorescent sensor for in vivo imaging of GABA

  • Mayrhofer JM, Haiss F, Helmchen F, Weber B (2015) Sparse, reliable, and long-term stable representation of periodic whisker deflections in the mouse barrel cortex. NeuroImage 115:52–63

    PubMed  Google Scholar 

  • McGinley MJ, Vinck M, Reimer J et al (2015) Waking state: rapid variations modulate neural and behavioral responses. Neuron 87:1143–1161

    CAS  PubMed  PubMed Central  Google Scholar 

  • McMahon SM, Jackson MB (2018) An inconvenient truth: calcium sensors are calcium buffers. Trends Neurosci 41:880–884

    CAS  PubMed  PubMed Central  Google Scholar 

  • McVea DA, Murphy TH, Mohajerani MH (2016) Large scale cortical functional networks associated with slow-wave and spindle-burst-related spontaneous activity. Front Neural Circuits 10:103

    PubMed  PubMed Central  Google Scholar 

  • Musall S, Kaufman MT, Juavinett AL, Gluf S, Churchland AK (2019) Single-trial neural dynamics are dominated by richly varied movements. Nat Neurosci 22:1677–1686

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nöbauer T, Skocek O, Pernía-Andrade AJ et al (2017) Video rate volumetric Ca imaging across cortex using seeded iterative demixing (SID) microscopy. Nat Methods 14:811–818

    PubMed  Google Scholar 

  • Ouzounov DG, Wang T, Wang M et al (2017) In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain. Nat Methods 14:388–390

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ovsepian SV (2019) The dark matter of the brain. Brain Struct Funct 224:973–983

    PubMed  Google Scholar 

  • Ovsepian SV, Olefir I, Westmeyer G et al (2017) Pushing the boundaries of neuroimaging with optoacoustics. Neuron 96:966–988

    CAS  PubMed  Google Scholar 

  • Pachitariu M, Stringer C, Harris KD (2018) Robustness of spike deconvolution for neuronal calcium imaging. J Neurosci Off J Soc Neurosci 38:7976–7985

    CAS  Google Scholar 

  • Paninski L, Cunningham JP (2018) Neural data science: accelerating the experiment-analysis-theory cycle in large-scale neuroscience. Curr Opin Neurobiol 50:232–241

    CAS  PubMed  Google Scholar 

  • Patel TP, Man K, Firestein BL, Meaney DF (2015) Automated quantification of neuronal networks and single-cell calcium dynamics using calcium imaging. J Neurosci Methods 243:26–38

    CAS  PubMed  PubMed Central  Google Scholar 

  • Patriarchi T, Cho JR, Merten K et al (2018) Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science 360:eaat442

    Google Scholar 

  • Peron SP, Freeman J, Iyer V et al (2015) A cellular resolution map of barrel cortex activity during tactile behavior. Neuron 86:783–799

    CAS  PubMed  Google Scholar 

  • Peters AJ, Chen SX, Komiyama T (2014) Emergence of reproducible spatiotemporal activity during motor learning. Nature 510:263–267

    CAS  PubMed  Google Scholar 

  • Piatkevich KD, Bensussen S, Tseng HA, Shroff SN, Lopez-Huerta VG, Park D, Jung EE, Shemesh OA, Straub C, Gritton HJ, Romano MF, Costa E, Sabatini BL, Fu Z, Boyden ES, Han X (2019) Population imaging of neural activity in awake behaving mice. Nature 574:413–417

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pilz G-A, Bottes S, Betizeau M et al (2018) Live imaging of neurogenesis in the adult mouse hippocampus. Science 359:658–662

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pnevmatikakis EA (2019) Analysis pipelines for calcium imaging data. Curr Opin Neurobiol 55:15–21

    CAS  PubMed  Google Scholar 

  • Pnevmatikakis EA, Soudry D, Gao Y et al (2016) Simultaneous denoising, deconvolution, and demixing of calcium imaging data. Neuron 89:285–299

    CAS  PubMed  PubMed Central  Google Scholar 

  • Poort J, Khan AG, Pachitariu M et al (2015) Learning enhances sensory and multiple non-sensory representations in primary visual cortex. Neuron 86:1478–1490

    CAS  PubMed  PubMed Central  Google Scholar 

  • Prakash R, Yizhar O, Grewe B et al (2012) Two-photon optogenetic toolbox for fast inhibition, excitation and bistable modulation. Nat Methods 9:1171–1179

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pryazhnikov E, Mugantseva E, Casarotto P et al (2018) Longitudinal two-photon imaging in somatosensory cortex of behaving mice reveals dendritic spine formation enhancement by subchronic administration of low-dose ketamine. Sci reports 8:6464

    Google Scholar 

  • Ramesh RN, Burgess CR, Sugden AU et al (2018) Intermingled ensembles in visual association cortex encode stimulus identity or predicted outcome. Neuron 100:900–915.e9

    CAS  PubMed  PubMed Central  Google Scholar 

  • Real R, Peter M, Trabalza A et al (2018) In vivo modeling of human neuron dynamics and Down syndrome. Science 362:eaau1810

    PubMed  PubMed Central  Google Scholar 

  • Romo R, de Lafuente V (2013) Conversion of sensory signals into perceptual decisions. Prog Neurobiol 103:41–75

    PubMed  Google Scholar 

  • Roome CJ, Kuhn B (2014) Chronic cranial window with access port for repeated cellular manipulations, drug application, and electrophysiology. Front Cell Neurosci 8:379

    PubMed  PubMed Central  Google Scholar 

  • Sadakane O, Masamizu Y, Watakabe A et al (2015) Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates. Cell reports 13:1989–1999

    CAS  PubMed  Google Scholar 

  • Sasaki T, Takahashi N, Matsuki N, Ikegaya Y (2008) Fast and accurate detection of action potentials from somatic calcium fluctuations. J Neurophysiol 100:1668–1676

    CAS  PubMed  Google Scholar 

  • Sato M, Kawano M, Yanagawa Y, Hayashi Y (2016) In vivo two-photon imaging of striatal neuronal circuits in mice. Neurobiol Learn Mem 135:146–151

    PubMed  Google Scholar 

  • Shoham S, O’Connor DH, Segev R (2006) How silent is the brain: is there a “dark matter” problem in neuroscience? J Comp Physiol Neuroethol sensory, neural, Behav Physiol 192:777–784

    Google Scholar 

  • Shuler MG, Bear MF (2006) Reward timing in the primary visual cortex. Sci 311:1606–1609

    CAS  Google Scholar 

  • Sofroniew NJ, Flickinger D, King J, Svoboda K (2016) A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging. Elife 5:e14472

    PubMed  PubMed Central  Google Scholar 

  • Song A, Charles AS, Koay SA et al (2017a) Volumetric two-photon imaging of neurons using stereoscopy (vTwINS). Nat Methods 14:420–426

    CAS  PubMed  PubMed Central  Google Scholar 

  • Song C, Barnes S, Knöpfel T (2017b) Mammalian cortical voltage imaging using genetically encoded voltage indicators: a review honoring professor Amiram Grinvald. Neurophotonics 4:031214

    PubMed  PubMed Central  Google Scholar 

  • Speiser A, Yan J, Archer EW, Buesing L, Turaga SC, Macke JH (2017) Fast amortized inference of neural activity from calcium imaging data with variational autoencoders. Advances in Neural Information Processing Systems 4024–4034

  • Spires TL, Meyer-Luehmann M, Stern EA et al (2005) Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci Off J Soc Neurosci 25:7278–7287

    CAS  Google Scholar 

  • Steinmetz NA, Buetfering C, Lecoq J, et al (2017) Aberrant cortical activity in multiple GCaMP6-expressing transgenic mouse lines

  • Steinmetz NA, Koch C, Harris KD, Carandini M (2018) Challenges and opportunities for large-scale electrophysiology with Neuropixels probes. Curr Opin Neurobiol 50:92–100

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stirman JN, Smith IT, Kudenov MW, Smith SL (2016) Wide field-of-view, multi-region, two-photon imaging of neuronal activity in the mammalian brain. Nat Biotechnol 34:857–862

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stringer C, Pachitariu M (2019) Computational processing of neural recordings from calcium imaging data. Curr Opin Neurobiol 55:22–31

    CAS  PubMed  Google Scholar 

  • Stringer C, Pachitariu M, Steinmetz N et al (2019) Spontaneous behaviors drive multidimensional, brainwide activity. Sci 364:255

    Google Scholar 

  • Takahashi N, Oertner TG, Hegemann P, Larkum ME (2016) Active cortical dendrites modulate perception. Science 354:1587–1590

    CAS  PubMed  Google Scholar 

  • Tervo DGR, Hwang B-Y, Viswanathan S et al (2016) A designer AAV variant permits efficient retrograde access to projection neurons. Neuron 92:372–382

    CAS  PubMed  PubMed Central  Google Scholar 

  • Theis L, Berens P, Froudarakis E et al (2016) Benchmarking spike rate inference in population calcium imaging. Neuron 90:471–482

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tian L, Hires SA, Looger LL (2012) Imaging neuronal activity with genetically encoded calcium indicators. Cold Spring Harb Protoc 2012:647–656

    PubMed  Google Scholar 

  • Trachtenberg JT, Chen BE, Knott GW et al (2002) Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420:788–794

    CAS  PubMed  Google Scholar 

  • Vanni MP, Chan AW, Balbi M et al (2017) Mesoscale mapping of mouse cortex reveals frequency-dependent cycling between distinct macroscale functional modules. J Neurosci Off J Soc Neurosci 37:7513–7533

    CAS  Google Scholar 

  • Voglewede RL, Vandemark KM, Davidson AM et al (2019) Reduced sensory-evoked structural plasticity in the aging barrel cortex. Neurobiol Aging 81:222–233

    PubMed  PubMed Central  Google Scholar 

  • Vogt N (2018) Machine learning in neuroscience. Nat methods 15:33

    CAS  Google Scholar 

  • Wang KH, Majewska A, Schummers J et al (2006) In vivo two-photon imaging reveals a role of arc in enhancing orientation specificity in visual cortex. Cell 126:389–402

    CAS  PubMed  Google Scholar 

  • Wekselblatt JB, Flister ED, Piscopo DM, Niell CM (2016) Large-scale imaging of cortical dynamics during sensory perception and behavior. J Neurophysiol 115:2852–2866

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xie Y, Chan AW, McGirr A et al (2016) Resolution of high-frequency mesoscale intracortical maps using the genetically encoded glutamate sensor iGluSnFR. J Neurosci Off J Soc Neurosci 36:1261–1272

    Google Scholar 

  • Xu Y, Zou P, Cohen AE (2017) Voltage imaging with genetically encoded indicators. Curr Opin Chem Biol 39:1–10

    PubMed  PubMed Central  Google Scholar 

  • Yamashita T, Pala A, Pedrido L et al (2013) Membrane potential dynamics of neocortical projection neurons driving target-specific signals. Neuron 80:1477–1490

    CAS  PubMed  Google Scholar 

  • Yang HH, St-Pierre F (2016) Genetically Encoded Voltage Indicators: opportunities and Challenges. J Neurosci Off J Soc Neurosci 36:9977–9989

    CAS  Google Scholar 

  • Yang W, Yuste R (2017) In vivo imaging of neural activity. Nat Methods 14:349–359

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang G, Pan F, Gan W-B (2009) Stably maintained dendritic spines are associated with lifelong memories. Nature 462:920–924

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yasuda R, Nimchinsky EA, Scheuss V et al (2004) Imaging calcium concentration dynamics in small neuronal compartments. Sci STKE 2004:pl5

    PubMed  Google Scholar 

  • Zhu L, Lee CR, Margolis DJ, Najafizadeh L (2018) Decoding cortical brain states from widefield calcium imaging data using visibility graph. Biomed Opt Express 9:3017–3036

    PubMed  PubMed Central  Google Scholar 

  • Ziv NE, Brenner N (2018) Synaptic tenacity or lack thereof: spontaneous remodeling of synapses. Trends Neurosci 41:89–99

    CAS  PubMed  Google Scholar 

  • Ziv Y, Burns LD, Cocker ED et al (2013) Long-term dynamics of CA1 hippocampal place codes. Nat Neurosci 16:264–266

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are supported by grants from the US National Institutes of Health (R01NS094450, DJM), US National Science Foundation (CBET-1605646, LN and DJM; IOS-1845355, DJM), and New Jersey Commission on Brain Injury Research (CBIR16IRG032, DJM and LN).

Author information

Authors and Affiliations

  1. Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

    Christian R. Lee & David J. Margolis

  2. Department of Electrical and Computer Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

    Laleh Najafizadeh

Authors
  1. Christian R. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laleh Najafizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David J. Margolis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J. Margolis.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, C.R., Najafizadeh, L. & Margolis, D.J. Investigating learning-related neural circuitry with chronic in vivo optical imaging. Brain Struct Funct 225, 467–480 (2020). https://doi.org/10.1007/s00429-019-02001-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-019-02001-9

Keywords

Search

Navigation