My laboratory is interested in two questions: the mechanisms of memory in the brain and the mechanisms of phototransduction in photoreceptors. In both cases, we seek to determine how chemical and electrical processes can work as a system to perform physiological function.

We are using the rat brain slice to study activity-dependent synaptic plasticity. Most recently, we found that plasticity is greatly heightened during a cholinergically-induced theta-frequency oscillation of the hippocampal network. As a step in this direction, we have developed a means of monitoring individual synapses in the dendrites using Ca²⁺-sensitive dyes and optical detection methods. Theoretical studies are also being done in an attempt to explore the possible relationship of brain oscillations to memory events. Most recently, it has become possible to test various theories by measuring oscillations from the brain surface of patients being treated for epilepsy. These patients are willing to do standard memory tests and we can directly measure what is going on in their brains during these tests.

A related question of interest is the molecular basis of memory. We have done theoretical work suggesting that the repository of synaptic memory may be the calcium/calmodulin dependent protein kinase II contained within a synaptic structure called the postsynaptic density. There is now substantial support for this model and we are attempting further tests. The processes of synaptic plasticity are not fixed, but rather can be altered by neuromodulators. Our recent work shows that dopamine can affect both the strengthening and weakening of synapses.

In the area of phototransduction, a central problem is the elucidation of the cascade reactions by which a single photon absorbed by rhodopsin activates thousands of channels. We have obtained evidence for the involvement of Ca²⁺ released by G protein, phospholipase-C, IP3 cascade. However, we have evidence that the channels are directly opened by cGMP. Thus, the current problem is to understand how cGMP might be generated by Ca²⁺. This marvelous cascade provides the opportunity to study other interesting reactions such as modulation of rhodopsin deactivation and the role of GTP hydrolysis.

Recent Publications:

Lisman JE. (2005) Hippocampus, II: memory connections. Am J Psychiatry. 162:239.

Jensen O, Lisman JE. (2005) Hippocampal sequence-encoding driven by a cortical multi-item working memory buffer. Trends Neurosci. 28:67-72. [abstract]

Otmakhov N, Tao-Cheng JH, Carpenter S, Asrican B, Dosemeci A, Reese TS, Lisman J. (2004) Persistent accumulation of calcium/calmodulin-dependent protein kinase II in dendritic spines after induction of NMDA receptor-dependent chemical long-term potentiation. J Neurosci. 24:9324-31. [abstract]

Otmakhova NA, Lisman JE. (2004) Contribution of Ih and GABAB to Synaptically Induced Afterhyperpolarizations in CA1: A Brake on the NMDA Response. J Neurophysiol. 92:2027-39 [abstract].

Raghavachari S, Lisman JE. (2004) Properties of Quantal Transmission at CA1 Synapses. J Neurophysiol. 92:2456-67 [abstract].

Garger AV, Richard EA, Lisman JE., (2004) The excitation cascade of Limulus ventral photoreceptors: guanylate cyclase as the link between InsP3-mediated Ca2+ release and the opening of cGMP-gated channels. BMC Neurosci. 5:7. [abstract]

Otmakhov N, Khibnik L, Otmakhova N, Carpenter S, Riahi S, Asrican B, Lisman J. (2004) Forskolin-Induced LTP in the CA1 Hippocampal Region Is NMDA Receptor Dependent. J Neurophysiol. 91:1955-62. [abstract]

Lisman J, Lichtman JW, Sanes JR. (2003) LTP: perils and progress. Nat Rev Neurosci. 4:926-9.

Lisman J. (2003) Actin's actions in LTP-induced synapse growth. Neuron. 38:361-2.

Lisman J. (2003) Long-term potentiation: outstanding questions and attempted synthesis. Philos Trans R Soc Lond B Biol Sci. 358:829-42. [abstract]

Kepecs, A., Lisman, J., (2003) Information encoding and computation with spikes and bursts., Network: Comput. Neural Syst. 14:103-118 [abstract].

Conti, R., Lisman, J.: The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: Evidence for multiquantal release, PNAS, April 15, 2003, 100(8):4885-4890 [abstract].

Graboi, D., Lisman, J., Recognition by top-down and bottom-up processing in cortex: the control of selective attention, April 17, 2003, Journal of Neurophysiology. [abstract]

Lisman, J., Long-term potentiation: Outstanding Questions/Attempted Synthesis, Philosophical Transactions of the Royal Society London B, (2003) 358, 829-842. [abstract]

Lisman, J.E., Richard, EA, Raghavachari, S, Payne, R.: Simultaneous roles for Ca2+ in excitation and adaptation of Limulus ventral photoreceptors, Advances in Experimental Medicine and Biology, 2002; 514:507-538. [abstract]

Koulakov, A.A., Raghavachari, S., Kepecs, A., Lisman, J.E.: Model for a Robust Neural Integrator., Nature Neuroscience, August 2002, 5(8):775-782. [abstract]

Jensen, O., Gelfand, J., Kounios, J., Lisman, J.E.: Oscillations in the Alpha Band (9-12 Hz) Increase with Memory Load during Retention in a Short-term Memory Task., Cerebral Cortex, August 2002, 12:877-882. [abstract]

Kepecs, A., Wang, X-J, Lisman, J., Bursting Neurons Signal Input Slope, The Journal of Neuroscience, October 15, 2002, 22(20):9053-9062. [abstract]

Conti, R, Lisman, J.: A Large Sustained Ca2+ Elevation Occurs in Unstimulated Spines During the LTP Pairing Protocol But Does Not Change Synaptic Strength, Hippocampus 12(5):667-679, 2002. [abstract]

Lisman, J.E., Schulman, H., and Cline, H. (2002) The Molecular Basis of CaMKII Function in Synaptic and Behavioural Memory. Nature Reviews Neuroscience, 3:175-190. [abstract]

Otmakhova, N.A., Otmakhov N., and Lisman, J.E. (2002) Pathway-Specific Properties of AMPA and NMDA-Mediated Transmission in CA1 Hippocampal Pyramidal Cells, The Journal of Neuroscience, 22:1199-1207. [abstract]

Otmakhov, N., Lisman, J.E. (2002) Postsynaptic Application of a cAMP Analogue Reverses Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons., Journal of Neurophysiology 87:3018-3032. [abstract]

Chen, H.X, Otmakhov, N., Strack, S., Colbran, R.J., and Lisman, J.E. (2001) Is Persistent Activity of Calcium/Calmodulin-Dependent Kinase Required for the Maintenance of LTP? Journal of Neurophysiology 85:1368-1376. [abstract]

Lisman, J.E. and Morris, G.M. (2001) Why is the cortex a slow learner? Nature - News and Views: 411:248-249.

Lisman, J., Jensen, O., and Kahana, M. (2001) In Neuronal Mechanisms of Memory Formation. (ed. Holscher, C.) 195-223 (Cambridge University Press, Cambridge, UK.

Garger, A., Richard, E., Lisman, J. (2001) Inhibitors of guanylate cyclase inhibit phototransduction in Limulus ventral photoreceptors. Visual Neuroscience, 18(4):625-32. [abstract]

Chen, F. H., Baumann, A., Payne, R., Lisman, J.E. (2001). A cGMP-gated channel subunit in Limulus photoreceptors. Visual Neuroscience, 18(4):517-26 [abstract]

Kim, C.H. and Lisman, J.E. (2001). A Labile Component of AMPA Receptor-Mediated Synaptic Transmission Is Dependent on Microtubule Motors, Actin, and N-Ethylmaleimide-Sensitive Factor. Journal of Neuroscience, 21:4188-4194. [abstract]

Raghavachari, S., Kahana, M., Rizzuto, D., Caplan, J., Kirschen, M., Bourgeois, B., Madsen, J., Lisman, J. (2001). Gating of Human Theta Oscillations by a Working Memory Task. Journal of Neuroscience, 21:3175-3183. [abstract]

Lisman, J.E. and Zhabotinsky, A. M. (2001). A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA-receptor anchoring assembly. Neuron, 31:191-201. [abstract]

Lisman, J.E. and Otmakhova, N.A. (2001). Storage, recall, and novelty detection of sequences by the hippocampus: elaborating on the SOCRATIC model to account for normal and aberrant effects of dopamine. Hippocampus, 11(5):551-68. [abstract]

Jensen O, Lisman JE. (2000) Position reconstruction from an ensemble of hippocampal place cells: contribution of theta phase coding. J Neurophysiol. 83(5):2602-9. [abstract]

Otmakhova NA, Otmakhov N, Mortenson LH, Lisman JE. (2000) Inhibition of the cAMP pathway decreases early long-term potentiation at CA1 hippocampal synapses. J Neurosci. 20(12):4446-51. [abstract]

Otmakhova NA, Lisman JE. (2000) Dopamine, serotonin, and noradrenaline strongly inhibit the direct perforant path-CA1 synaptic input, but have little effect on the Schaffer collateral input. Ann N Y Acad Sci. 911:462-4.

Kovalchuk, Y., Eilers, J., Lisman, J. And Konnerth, A. (2000) NMDA receptor-mediated subthreshold Ca2+ signals in spines of hippocampal neurons. Journal of Neuroscience 20:1791-1799.

Otmakhova, N.A. and Lisman, J.E. (1999) Dopamine selectively inhibits the direct cortical pathway to the CA1 hippocampal region. J. Neuroscience 19:1437-1445. [abstract]

Lisman, J.E. (1999) Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate-CA3 interaction. Neuron 22:233-242. [abstract]

Chen HX, Otmakhov N, Lisman J. (1999) Requirements for LTP induction by pairing in hippocampal CA1 pyramidal cells. J Neurophysiol. 82(2):526-32. [abstract]

Kim CH, Lisman JE. (1999) A role of actin filament in synaptic transmission and long-term potentiation. J Neurosci. 19(11):4314-24. [abstract]

Lisman JE, Fellous JM, Wang XJ. (1998) A role for NMDA-receptor channels in working memory. Nat Neurosci. 1(4):273-5.

Lisman, J. (1997) Bursts as a unit of neural information: making unreliable synapses reliable. Trends In Neuroscience 20:38-43. [abstract]

Otmakhova, N. and Lisman, J.E. (1996) D1/D5 dopamine receptor activation increases the magnitude of early long-term potentiation at CA1 hippocampal synapses. J. Neuroscience 16:7478-7486. [abstract]

Lisman, J. and Idiart, M.A.P. (1995) Storage of 7 ± 2 short-term memories in oscillatory subcycles. Science 267:1512-1515. [abstract]

Lisman, J., (1994) The CaM kinase II hypothesis for the storage of synaptic memory. TINS 17: 406-412. [abstract]

Huerta, P.T., and Lisman, J.E. (1993) Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature 364: 723-725. [abstract]

Shin, J., Richard, E.A., and Lisman, J.E. (1993) Ca²⁺ is an obligatory intermediate in the excitation cascade of Limulus photoreceptors. Neuron 11: 845-855. [abstract]