John Lisman, Ph.D.
Professor of Biology
Amplification and Switching in
Signal Transduction and Memory
Ph.D., Massachusetts Institute of Technology
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.
- Asrican B, Lisman J, Otmakhov N. Synaptic strength of individual spines correlates with bound Ca2+-calmodulin-dependent kinase II. J Neurosci 2007;27(51):14007-11..
- de Almeida L, Idiart M, Lisman JE. Memory retrieval time and memory capacity of the CA3 network: role of gamma frequency oscillations. Learn Mem 2007;14(11):795-806. [full text in PubMed Central]
- Lisman JE. Finding our rhythm. Nat Neurosci 2007;10(4):395..
- Lisman JE. Role of the dual entorhinal inputs to hippocampus: a hypothesis based on cue/action (non-self/self) couplets. Prog Brain Res 2007;163:615-818..
- Lisman JE, Raghavachari S, Tsien RW. The sequence of events that underlie quantal transmission at central glutamatergic synapses. Nat Rev Neurosci 2007;8(8):597-609..
- Mullasseril P, Dosemeci A, Lisman JE, Griffith LC. A structural mechanism for maintaining the 'on-state' of the CaMKII memory switch in the post-synaptic density. J Neurochem 2007;103(1):357-64. [full text in PubMed Central]
- Sanhueza M, McIntyre CC, Lisman JE. Reversal of synaptic memory by Ca2+/calmodulin-dependent protein kinase II inhibitor. J Neurosci 2007;27(19):5190-9..
- Lisman J, Buzsaki G. A neural coding scheme formed by the combined function of gamma and theta oscillations. Schizophr Bull 2008;34(5):974-80. [full text in PubMed Central]
- Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 2008;31(5):234-42. [full text in PubMed Central]
- Pi HJ, Lisman JE. Coupled phosphatase and kinase switches produce the tristability required for long-term potentiation and long-term depression. J Neurosci 2008;28(49):13132-8. [full text in PubMed Central]
- Zhang Y, Behrens MM, Lisman JE. Prolonged exposure to NMDAR antagonist suppresses inhibitory synaptic transmission in prefrontal cortex. J Neurophysiol 2008;100(2):959-65. [full text in PubMed Central]
- de Almeida L, Idiart M, Lisman JE. The input-output transformation of the hippocampal granule cells: from grid cells to place fields. J Neurosci 2009;29(23):7504-12. [full text in PubMed Central]
- de Almeida L, Idiart M, Lisman JE. A second function of gamma frequency oscillations: an E%-max winner-take-all mechanism selects which cells fire. J Neurosci 2009;29(23):7497-503. [full text in PubMed Central]
- Erickson MA, Maramara LA, Lisman J. A Single 2-Spike Burst Induces GluR1-dependent Associative Short-term Potentiation: A Potential Mechanism for Short-term Memory. J Cogn Neurosci 2009..
- Lisman J, Redish AD. Prediction, sequences and the hippocampus. Philos Trans R Soc Lond B Biol Sci 2009;364(1521):1193-201. [full text in PubMed Central]
- Lisman JE. The pre/post LTP debate. Neuron 2009;63(3):281-4..
- Zhang Y, Llinas RR, Lisman JE. Inhibition of NMDARs in the Nucleus Reticularis of the Thalamus Produces Delta Frequency Bursting. Front Neural Circuits 2009;3:20. [full text in PubMed Central]
- de Almeida L, Idiart M, Lisman JE. The single place fields of CA3 cells: A two-stage transformation from grid cells. Hippocampus 2010..
- Erickson MA, Maramara LA, Lisman J. A Single Brief Burst Induces GluR1-dependent Associative Short-term Potentiation: A Potential Mechanism for Short-term Memory. Journal of Cognitive Neuroscience. 2010;22(11):2530-40. PMID: ISI:000279976300011.
- Lisman J. Working memory: the importance of theta and gamma oscillations. Curr Biol 2010;20(11):R490-2..
- Lisman J. Formation of the nonfunctional and functional pools of granule cells in the dentate gyrus: role of neurogenesis, LTP and LTD. J Physiol 2010..
- Lisman JE, Pi HJ, Zhang Y, Otmakhova NA. A thalamo-hippocampal-ventral tegmental area loop may produce the positive feedback that underlies the psychotic break in schizophrenia. Biol Psychiatry 2010;68(1):17-24..
- Pi HJ, Otmakhov N, El Gaamouch F, Lemelin D, De Koninck P, Lisman J. CaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action. Proc Natl Acad Sci U S A 2010;107(32):14437-42. [full text in PubMed Central]
- Pi HJ, Otmakhov N, Lemelin D, De Koninck P, Lisman J. Autonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation. J Neurosci 2010;30(26):8704-9. [full text in PubMed Central]
- Renno-Costa C, Lisman JE, Verschure PF. The mechanism of rate remapping in the dentate gyrus. Neuron 2010;68(6):1051-8. [full text in PubMed Central]
- Faas GC, Raghavachari S, Lisman JE, Mody I. Calmodulin as a direct detector of Ca(2+) signals. Nat Neurosci 2011..
Last edit: Sept. 1, 2011