Frequency Facilitation at Mossy Fiber–CA3 Synapses of Freely Behaving Rats Contributes to the Induction of Persistent LTD via an Adenosine-A1 Receptor-Regulated Mechanism

Frequency facilitation (FF), comprising a rapid and multiple-fold increase in the magnitude of evoked field potentials, is elicited by low-frequency stimulation (LFS) at mossy fiber–CA3 synapses. Here, we show that in freely behaving rats, FF reliably occurs in response to 1 and 2Hz but not in response to 0.25-, 0.3-, or 0.5-Hz LFS. Strikingly, prolonged (∼600 s) FF was tightly correlated to the induction of long-term depression (LTD) in freely moving animals. Although LFS at 2 Hz elicited unstable FF and unstable LTD, application of LFS at 1 Hz elicited pronounced FF, as well as robust LTD that persisted for over 24 h. This correlation of prolonged FF with LTD was absent at stimulation frequencies that did not induce FF. The adenosine-A1 receptor appears to participate in these effects: Application of adenosine-A1, but not adenosine-A3, receptor antagonists enhanced mossy fiber synaptic transmission and occluded FF. Furthermore, adenosine-A1 receptor antagonism resulted in more stable FF at 1 or 2 Hz and elicited more potent LTD. These data support the fact that FF contributes to the enablement of long-term information storage at mossy fiber–CA3 synapses and that the adenosine-A1 receptor may regulate the thresholds for this process

Enhancing Interdisciplinary, Mathematics, and Physical Science in an Undergraduate Life Science Program through Physical Chemistry

BIO2010 advocates enhancing the interdisciplinary, mathematics, and physical science components of the undergraduate biology curriculum. The Department of Chemistry and Life Science at West Point responded by developing a required physical chemistry course tailored to the interests of life science majors. To overcome student resistance to physical chemistry, students were enabled as long-term stakeholders who would shape the syllabus by selecting life science topics of interest to them. The initial 2 yr of assessment indicates that students have a positive view of the course, feel they have succeeded in achieving course outcome goals, and that the course is relevant to their professional future. Instructor assessment of student outcome goal achievement via performance on exams and labs is comparable to that of students in traditional physical chemistry courses. Perhaps more noteworthy, both student and instructor assessment indicate positive trends from year 1 to year 2, presumably due to the student stakeholder effect

PTP and LTP at a hippocampal mossy fiber-interneuron synapse

The mossy fiber-CA3 pyramidal neuron synapse is a main component of the hippocampal trisynaptic circuitry. Recent studies, however, suggested that inhibitory interneurons are the major targets of the mossy fiber system. To study the regulation of mossy fiber-interneuron excitation, we examined unitary and compound excitatory postsynaptic currents in dentate gyrus basket cells, evoked by paired recording between granule and basket cells or extracellular stimulation of mossy fiber collaterals. The application of an associative high-frequency stimulation paradigm induced posttetanic potentiation (PTP) followed by homosynaptic long-term potentiation (LTP). Analysis of numbers of failures, coefficient of variation, and paired-pulse modulation indicated that both PTP and LTP were expressed presynaptically. The Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) did not affect PTP or LTP at a concentration of 10 mM but attenuated LTP at a concentration of 30 mM. Both forskolin, an adenylyl cyclase activator, and phorbolester diacetate, a protein kinase C stimulator, lead to a long-lasting increase in excitatory postsynaptic current amplitude. H-89, a protein kinase A inhibitor, and bisindolylmaleimide, a protein kinase C antagonist, reduced PTP, whereas only bisindolylmaleimide reduced LTP. These results may suggest a differential contribution of protein kinase A and C pathways to mossy fiber-interneuron plasticity. Interneuron PTP and LTP may provide mechanisms to maintain the balance between synaptic excitation of interneurons and that of principal neurons in the dentate gyrus-CA3 network

The 5' Cap of Tobacco Mosaic Virus (TMV) Is Required for Virion Attachment to the Actin/Endoplasmic Reticulum Network During Early Infection

Almost nothing is known of the earliest stages of plant virus infections. To address this, we microinjected Cy3 (UTP)-labelled tobacco mosaic virus (TMV) into living tobacco trichome cells. The Cy3-virions were infectious, and the viral genome trafficked from cell to cell. However, neither the fluorescent vRNA pool nor the co-injected green fluorescent protein (GFP) left the injected trichome, indicating that the synthesis of (unlabelled) progeny viral (v)RNA is required to initiate cell-to-cell movement, and that virus movement is not accompanied by passive plasmodesmatal gating. Cy3-vRNA formed granules that became anchored to the motile cortical actin/endoplasmic reticulum (ER) network within minutes of injection. Granule movement on actin/ER was arrested by actin inhibitors indicating actin-dependent RNA movement. The 5' methylguanosine cap was shown to be required for vRNA anchoring to the actin/ER. TMV vRNA lacking the 5' cap failed to form granules and was degraded in the cytoplasm. Removal of the 3' untranslated region or replicase both inhibited replication but did not prevent granule formation and movement. Dual-labelled TMV virions in which the vRNA and the coat protein were highlighted with different fluorophores showed that both fluorescent signals were initially located on the same ER-bound granules, indicating that TMV virions may become attached to the ER prior to uncoating of the viral genome.</p