Skip to main content

Using “Hard” Real-Time Dynamic Clamp to Study Cellular and Network Mechanisms of Synchronization in the Hippocampal Formation

  • Chapter
  • First Online:
Dynamic-Clamp

Part of the book series: Springer Series in Computational Neuroscience ((NEUROSCI,volume 1))

  • 694 Accesses

Abstract

We report on development and use of dynamic-clamp technology to understand how synchronous neuronal activity is generated in the hippocampus and entorhinal cortex. We find that “hard” real-time dynamic-clamp systems, characterized by very small maximal errors in timing of feedback, are necessary for cases in which fast voltage-gated channels are being mimicked in experiments. Using a hard real-time system to study cellular oscillations in entorhinal cortex, we demonstrate that the stochastic gating of persistent Na+ channels is necessary for cellular oscillations, and that cellular oscillations lead to dynamic changes in gain for conductance-based synaptic inputs. At the network level, we review experiments demonstrating that oscillating entorhinal stellate cells synchronize best via mutually excitatory interactions. Next, we show that cellular oscillations are volatile in the hypothesized “high-conductance” state, thought to occur in vivo, and suggest alternate means by which coherent activity can be generated in the absence of strong cellular oscillations. We close by discussing future developments that will increase the utility and widespread use of the dynamic-clamp method.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 269.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acker CD, Kopell N, White JA (2003) Synchronization of strongly coupled excitatory neurons: relating network behavior to biophysics. J Comput Neurosci 15:71–90.

    Article  PubMed  Google Scholar 

  • Alonso A, Llinas RR (1989) Subthreshold Na+-dependent theta-like rhythmicity in stellate cells of entorhinal cortex layer II. Nature 342:175–177.

    Article  PubMed  CAS  Google Scholar 

  • Alonso A, Klink R (1993) Differential electroresponsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer II. J Neurophysiol 70:128–143.

    PubMed  CAS  Google Scholar 

  • Banks MI, Li TB, Pearce RA (1998) The synaptic basis of GABAA,slow. J Neurosci 18:1305–1317.

    PubMed  CAS  Google Scholar 

  • Bettencourt JC, Lillis KP, Stupin LR, White JA (2008) Effects of imperfect dynamic clamp: Computational and experimental results. J Neurosci Methods 169:282–289.

    Article  PubMed  Google Scholar 

  • Bland BH, Colom LV (1993) Extrinsic and intrinsic properties underlying oscillation and synchrony in limbic cortex. Prog Neurobiol 41:157–208.

    Article  PubMed  CAS  Google Scholar 

  • Borg-Graham LJ, Monier C, Fregnac Y (1998) Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 393:369–373.

    Article  PubMed  CAS  Google Scholar 

  • Burgess N, Barry C, O’Keefe J (2007) An oscillatory interference model of grid cell firing. Hippocampus 17:801–812.

    Article  PubMed  Google Scholar 

  • Butera RJ, Jr., Wilson CG, Delnegro CA, Smith JC (2001) A methodology for achieving high-speed rates for artificial conductance injection in electrically excitable biological cells. IEEE Trans Biomed Eng 48:1460–1470.

    Article  PubMed  Google Scholar 

  • Buzsáki G (2002) Theta oscillations in the hippocampus. Neuron 33:325–340.

    Article  PubMed  Google Scholar 

  • Canavier CC, Butera RJ, Dror RO, Baxter DA, Clark JW, Byrne JH (1997) Phase response characteristics of model neurons determine which patterns are expressed in a ring circuit model of gait generation. Biol Cybern 77:367–380.

    Article  PubMed  CAS  Google Scholar 

  • Chow CC, White JA, Ritt J, Kopell N (1998) Frequency control in synchronized networks of inhibitory neurons. J Comput Neurosci 5:407–420.

    Article  PubMed  CAS  Google Scholar 

  • Christini DJ, Stein KM, Markowitz SM, Lerman BB (1999) Practical real-time computing system for biomedical experiment interface. Ann Biomed Eng 27:180–186.

    Article  PubMed  CAS  Google Scholar 

  • Destexhe A, Pare D (1999) Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. J Neurophysiol 81:1531–1547.

    PubMed  CAS  Google Scholar 

  • Destexhe A, Rudolph M, Pare D (2003) The high-conductance state of neocortical neurons in vivo. Nat Rev Neurosci 4:739–751.

    Article  PubMed  CAS  Google Scholar 

  • Dickson CT, Magistretti J, Shalinsky MH, Fransen E, Hasselmo ME, Alonso A (2000) Properties and role of I(h) in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons. J Neurophysiol 83:2562–2579.

    PubMed  CAS  Google Scholar 

  • Dorval AD, White JA (2005) Channel noise is essential for perithreshold oscillations in entorhinal stellate neurons. J Neurosci 25:10025–10028.

    Article  PubMed  CAS  Google Scholar 

  • Dorval AD, White JA (2006) Synaptic input statistics tune the variability and reproducibility of neuronal responses. Chaos 16:026105.

    Article  PubMed  Google Scholar 

  • Dorval AD, Christini DJ, White JA (2001) Real-time Linux dynamic clamp: a fast and flexible way to construct virtual ion channels in living cells. Ann Biomed Eng 29:897–907.

    Article  PubMed  CAS  Google Scholar 

  • Erchova I, Kreck G, Heinemann U, Herz AV (2004) Dynamics of rat entorhinal cortex layer II and III cells: characteristics of membrane potential resonance at rest predict oscillation properties near threshold. J Physiol 560:89–110.

    Article  PubMed  CAS  Google Scholar 

  • Ermentrout B, Kopell N (1991) Multiple pulse interactions and averaging in systems of coupled oscillators. J Math Biol 29:195–217.

    Article  Google Scholar 

  • Fernandez FR, White JA (2008) Artificial synaptic conductances reduce subthreshold oscillations and periodic firing in stellate cells of the entorhinal cortex. J Neurosci 28:3790–3803.

    Article  PubMed  CAS  Google Scholar 

  • Fransen E, Alonso AA, Dickson CT, Magistretti J, Hasselmo ME (2004) Ionic mechanisms in the generation of subthreshold oscillations and action potential clustering in entorhinal layer II stellate neurons. Hippocampus 14:368–384.

    Article  PubMed  CAS  Google Scholar 

  • Gillies MJ, Traub RD, LeBeau FE, Davies CH, Gloveli T, Buhl EH, Whittington MA (2002) A model of atropine-resistant theta oscillations in rat hippocampal area CA1. J Physiol 543:779–793.

    Article  PubMed  CAS  Google Scholar 

  • Giocomo LM, Zilli EA, Fransen E, Hasselmo ME (2007) Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing. Science 315:1719–1722.

    Article  PubMed  CAS  Google Scholar 

  • Gloor P (1997) The temporal lobe and limbic system. New York: Oxford University Press.

    Google Scholar 

  • Gloveli T, Dugladze T, Saha S, Monyer H, Heinemann U, Traub RD, Whittington MA, Buhl EH (2005a) Differential involvement of oriens/pyramidale interneurones in hippocampal network oscillations in vitro. J Physiol 562:131–147.

    Google Scholar 

  • Gloveli T, Dugladze T, Rotstein HG, Traub RD, Monyer H, Heinemann U, Whittington MA, Kopell NJ (2005b) Orthogonal arrangement of rhythm-generating microcircuits in the hippocampus. Proc Natl Acad Sci USA 102:13295–13300.

    Google Scholar 

  • Haas JS, White JA (2002) Frequency selectivity of layer II stellate cells in the medial entorhinal cortex. J Neurophysiol 88:2422–2429.

    Article  PubMed  Google Scholar 

  • Haas JS, Dorval AD, II, White JA (2007) Contributions of Ih to feature selectivity in layer II stellate cells of the entorhinal cortex. J Comput Neurosci 22:161–171.

    Article  PubMed  Google Scholar 

  • Hansel D, Mato G, Meunier C (1995) Synchrony in excitatory neural networks. Neural Comput 7:307–337.

    Article  PubMed  CAS  Google Scholar 

  • Hasselmo ME, Giocomo LM, Zilli EA (2007) Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons. Hippocampus 17:1252–1271.

    Article  PubMed  Google Scholar 

  • Hille B (2001) Ion channels of excitable membranes, 3rd Edition. Sunderland, Mass.: Sinauer.

    Google Scholar 

  • Hughes SW, Lorincz M, Cope DW, Crunelli V (2008) NeuReal: An interactive simulation system for implementing artificial dendrites and large hybrid networks. J Neurosci Methods 169:290–301.

    Article  PubMed  Google Scholar 

  • Kispersky TJ, White JA (2008) Stochastic models of ion channel gating. Scholarpedia 3:1327.

    Article  Google Scholar 

  • Klink R, Alonso A (1993) Ionic mechanisms for the subthreshold oscillations and differential electroresponsiveness of medial entorhinal cortex layer II neurons. J Neurophysiol 70:144–157.

    PubMed  CAS  Google Scholar 

  • Kullmann PH, Wheeler DW, Beacom J, Horn JP (2004) Implementation of a fast 16-Bit dynamic clamp using LabVIEW-RT. J Neurophysiol 91:542–554.

    Article  PubMed  Google Scholar 

  • Maccaferri G, Roberts JD, Szucs P, Cottingham CA, Somogyi P (2000) Cell surface domain specific postsynaptic currents evoked by identified GABAergic neurones in rat hippocampus in vitro. J Physiol 524 Pt 1:91–116.

    Google Scholar 

  • Milescu LS, Yamanishi T, Ptak K, Mogri MZ, Smith JC (2008) Real-time kinetic modeling of voltage-gated ion channels using dynamic clamp. Biophys J 95:66–87.

    Google Scholar 

  • Netoff TI, Acker CD, Bettencourt JC, White JA (2005a) Beyond two-cell networks: experimental measurement of neuronal responses to multiple synaptic inputs. J Comput Neurosci 18:287–295.

    Google Scholar 

  • Netoff TI, Banks MI, Dorval AD, Acker CD, Haas JS, Kopell N, White JA (2005b) Synchronization in hybrid neuronal networks of the hippocampal formation. J Neurophysiol 93:1197–1208.

    Google Scholar 

  • O'Keefe J (1993) Hippocampus, theta, and spatial memory. Curr Opin Neurobiol 3:917–924.

    Article  PubMed  Google Scholar 

  • O’Keefe J, Burgess N (2005) Dual phase and rate coding in hippocampal place cells: theoretical significance and relationship to entorhinal grid cells. Hippocampus 15:853–866.

    Article  PubMed  Google Scholar 

  • Pike FG, Goddard RS, Suckling JM, Ganter P, Kasthuri N, Paulsen O (2000) Distinct frequency preferences of different types of rat hippocampal neurones in response to oscillatory input currents. J Physiol 529 Pt 1:205–213.

    Google Scholar 

  • Pinto RD, Elson RC, Szucs A, Rabinovich MI, Selverston AI, Abarbanel HD (2001) Extended dynamic clamp: controlling up to four neurons using a single desktop computer and interface. J Neurosci Methods 108:39–48.

    Article  PubMed  CAS  Google Scholar 

  • Robinson HP, Kawai N (1993) Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J Neurosci Meth 49:157–165.

    Article  CAS  Google Scholar 

  • Rotstein HG, Pervouchine DD, Acker CD, Gillies MJ, White JA, Buhl EH, Whittington MA, Kopell N (2005) Slow and fast inhibition and an H-current interact to create a theta rhythm in a model of CA1 interneuron network. J Neurophysiol 94:1509–1518.

    Article  PubMed  Google Scholar 

  • Schreiber S, Erchova I, Heinemann U, Herz AV (2004) Subthreshold resonance explains the frequency-dependent integration of periodic as well as random stimuli in the entorhinal cortex. J Neurophysiol 92:408–415.

    Article  PubMed  Google Scholar 

  • Sharp AA, O’Neil MB, Abbott LF, Marder E (1993) Dynamic clamp: Computer-generated conductances in real neurons. J Neurophysiol 69:992–995.

    PubMed  CAS  Google Scholar 

  • Shoham S, O'Connor DH, Sarkisov DV, Wang SS (2005) Rapid neurotransmitter uncaging in spatially defined patterns. Nat Methods 2:837–843.

    Article  PubMed  CAS  Google Scholar 

  • Sohal VS, Huguenard JR (2005) Inhibitory coupling specifically generates emergent gamma oscillations in diverse cell types. Proc Natl Acad Sci USA 102:18638–18643.

    Article  PubMed  CAS  Google Scholar 

  • Vida I, Bartos M, Jonas P (2006) Shunting inhibition improves robustness of gamma oscillations in hippocampal interneuron networks by homogenizing firing rates. Neuron 49:107–117.

    Article  PubMed  CAS  Google Scholar 

  • Wang XJ, Buzsáki G (1996) Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model. J Neurosci 16:6402–6413.

    PubMed  CAS  Google Scholar 

  • White JA, Budde T, Kay AR (1995) A bifurcation analysis of neuronal subthreshold oscillations. Biophys J 69:1203–1217.

    Article  PubMed  CAS  Google Scholar 

  • White JA, Klink R, Alonso A, Kay AR (1998a) Noise from voltage-gated ion channels may influence neuronal dynamics in the entorhinal cortex. J Neurophysiol 80:262–269.

    Google Scholar 

  • White JA, Chow CC, Ritt J, Soto-Trevino C, Kopell N (1998b) Synchronization and oscillatory dynamics in heterogeneous, mutually inhibited neurons. J Comput Neurosci 5:5–16.

    Google Scholar 

  • White JA, Rubinstein JT, Kay AR (2000a) Channel noise in neurons. Trends Neurosci 23:131–137.

    Google Scholar 

  • White JA, Banks MI, Pearce RA, Kopell NJ (2000b) Networks of interneurons with fast and slow gamma-aminobutyric acid type A (GABAA) kinetics provide substrate for mixed gamma-theta rhythm. Proc Natl Acad Sci USA 97:8128–8133.

    Google Scholar 

Download references

Acknowledgments

We thank past and present students and collaborators on dynamic-clamp work, including M.I. Banks, J.C. Bettencourt, M. Binder, R.J. Butera, D.J. Christini, A.D. Dorval, E. Idoux, K.P. Lillis, N. Kopell, L.E. Moore, T.I. Netoff, P. Randeria , and L. Stupin. This work was supported by grants from the National Institutes of Health (NCRR, NIMH, and NINDS).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John A. White .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

White, J.A., Fernandez, F.R., Economo, M.N., Kispersky, T.J. (2009). Using “Hard” Real-Time Dynamic Clamp to Study Cellular and Network Mechanisms of Synchronization in the Hippocampal Formation. In: Bal, T., Destexhe, A. (eds) Dynamic-Clamp. Springer Series in Computational Neuroscience, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89279-5_9

Download citation

Publish with us

Policies and ethics