Craig Jahr, Ph.D.
Craig Jahr is a senior scientist in the Vollum Institute. After earning his B.A. degree in Psychology from the University of California at Riverside, Jahr studied Biology at the University of California at Santa Barbara. His Ph.D. in Pharmacology was awarded by the University of California at San Francisco in 1980. Jahr did postdoctoral research at UCSF and Harvard Medical School. He was appointed as an associate research scientist in Molecular Neurobiology at Yale University School of Medicine in 1985 and remained there until his appointment to the Vollum Institute in 1987.
Summary of Current Research
Neurons in the brain transmit information to each other through specialized connections called synapses. Craig Jahr and his coworkers use electrophysiological and optical techniques to focus on synaptic transmission involving the release of glutamate, a chemical neurotransmitter used at the vast majority of excitatory synapses in the CNS. The excitation is generated by the binding of glutamate to specific receptors embedded in the neuronal membrane.
Glutamate, like most other neurotransmitters, is released from presynaptic sites following action potential invasion by the fusion of transmitter-filled vesicles to the presynaptic membrane. A widely held belief in neurobiology is that a maximum of a single vesicle can be released per synapse per action potential. Jahr and coworkers have shown that, at certain synapses in the cerebellum and hippocampus, a single action potential can evoke the release of several vesicles per synapse per action potential. This results in a very high concentration of glutamate in the synapse that can saturate the postsynaptic receptors and ensures excitation of the postsynaptic neuron. In addition, it appears that vesicular release can occur not only at the presynaptic active zone, but also from other presynaptic locations that are not associated with postsynaptic specializations. Such ectopic release results in more rapid and complete activation of extrasynaptic receptors and may be necessary to maintain glial membranes close to synapses.
Jahr and his colleagues have found that glutamate released from the presynaptic terminal is cleared from the cleft very rapidly, within 2 to 3 milliseconds, despite a lack of an extracellular glutamate-degrading enzyme. Ultimately, released glutamate is taken up into neurons and surrounding astrocytes by glutamate transporters, membrane-spanning proteins that transport extracellular glutamate into cells. Jahr and coworkers have shown that glutamate transporters bind extracellular glutamate very rapidly and then translocate the neurotransmitter into cells, primarily astrocytes. In addition, they have shown that glutamate transporter blockers can prolong the postsynaptic effects of glutamate release, suggesting that glutamate uptake is important for normal synaptic function. Despite this, recent work in the lab suggests that altering the strength of neuronal uptake may determine whether perisynaptically located receptors, such as metabotropic glutamate receptors, are activated by synaptic release.
Sun W, Hansen KB, Jahr CE. (2017) Allosteric interactions between NMDA receptor subunits shape the developmental shift in channel properties. Neuron 94:58-64.e3.
Chiu DN, Jahr CE. (2017) Extracellular glutamate in the nucleus accumbens is nanomolar in both synaptic and non-synaptic compartments. Cell Reports 18:2576-2583.
Carter BC, Jahr CE. (2016) Postsynaptic, not presynaptic NMDA receptors are required for spike-timing-dependent LTD induction. Nature Neurosci. 19:1218-1224.
Pugh JR, Jahr CE. (2013) Activation of axonal receptors by GABA spillover increases somatic firing. J. Neurosci. 33:16924-16929.
Nahir B, Jahr CE. (2013) Activation of extrasynaptic NMDARs at individual parallel fiber–molecular layer interneuron synapses in cerebellum. J. Neurosci. 33:16323-16333.
Pugh JR, Jahr CE. (2011) Axonal GABAA receptors increase cerebellar granule cell excitability and synaptic activity. J. Neurosci. 31:565-574.
Christie JM, Chiu DN, Jahr CE. (2011) Ca(2+)-dependent enhancement of release by subthreshold somatic depolarization. Nature Neurosci. 14:62-68.
Christie JM and Jahr CE. (2009) Selective expression of ligand-gated ion channels in L5 pyramidal cell axons. J. Neurosci. 29:11441-11450.
Bender VA, Pugh JR and Jahr CE. (2009) Presynaptically expressed long-term potentiation increases multivesicular release at parallel fiber synapses. J. Neurosci. 29:10974-10978.
Christie JM and Jahr CE. (2008) Dendritic NMDA receptors activate axonal calcium channels. Neuron 60:298-307.
Herman MA and Jahr CE. (2007) Extracellular glutamate concentration in hippocampal slice. J. Neurosci. 27:9736-9741.
Piet R and Jahr CE. (2007) Glutamatergic and purinergic receptor-mediated calcium transients in Bergmann glial cells. J. Neurosci. 27:4027-4035.
Christie JM and Jahr CE. (2006) Multivesicular release at Schaffer collateral-CA1 hippocampal synapses. J. Neurosci. 26:210-216.
Wadiche JI and Jahr CE. (2005) Patterned expression of EAAT4 controls synaptic plasticity. Nature Neurosci. 8:1329-1334.
Matsui K and Jahr CE. (2004) Differential control of synaptic and ectopic vesicular release of glutamate. J. Neurosci. 24:8932-8939.
Matsui K and Jahr CE. (2003) Ectopic release of synaptic vesicles. Neuron 40:1173-1183.
Bergles DE, Tzingounis AV, and Jahr CE. (2002) Comparison of coupled and uncoupled currents during glutamate uptake by GLT-1 transporters. J. Neurosci. 22:10153-10162.
Wadiche JI and Jahr CE. (2001) Multivesicular release at climbing fiber-Purkinje cell synapses. Neuron 32:301-313.