@article{3622, abstract = {The extent of genetic variation in fitness and its components and genetic variation's dependence on environmental conditions remain key issues in evolutionary biology. We present measurements of genetic variation in preadult viability in a laboratory-adapted population of Drosophila melanogaster, made at four different densities. By crossing flies heterozygous for a wild-type chromosome and one of two different balancers (TM1, TM2), we measure both heterozygous (TM1/+, TM2/+) and homozygous (+/+) viability relative to a standard genotype (TM1/TM2). Forty wild-type chromosomes were tested, of which 10 were chosen to be homozygous viable. The mean numbers produced varied significantly between chromosome lines, with an estimated between-line variance in loge numbers of 0.013. Relative viabilities also varied significantly across chromosome lines, with a variance in loge homozygous viability of 1.76 and of loge heterozygous viability of 0.165. The between-line variance for numbers emerging increased with density, from 0.009 at lowest density to 0.079 at highest. The genetic variance in relative viability increases with density, but not significantly. Overall, the effects of different chromosomes on relative viability were remarkably consistent across densities and across the two heterozygous genotypes (TM1, TM2). The 10 lines that carried homozygous viable wild-type chromosomes produced significantly more adults than the 30 lethal lines at low density and significantly fewer adults at the highest density. Similarly, there was a positive correlation between heterozygous viability and mean numbers at low density, but a negative correlation at high density.}, author = {Gardner, Michael and Fowler, Kevin and Patridge, Linda and Barton, Nicholas H}, issn = {0014-3820}, journal = {Evolution}, number = {8}, pages = {1609 -- 1620}, publisher = {Wiley-Blackwell}, title = {{Genetic variation for preadult viability in Drosophila melanogaster}}, doi = {10.1111/j.0014-3820.2001.tb00680.x}, volume = {55}, year = {2001}, } @misc{3596, author = {Barton, Nicholas H}, booktitle = {Trends in Genetics}, issn = {0168-9479}, pages = {420 -- 420}, publisher = {Elsevier}, title = {{Mendel and mathematics}}, doi = {10.1016/S0168-9525(01)02315-0}, volume = {17}, year = {2001}, } @article{3546, abstract = {Local versus distant coherence of hippocampal CA1 pyramidal cells was investigated in the behaving rat. Temporal cross-correlation of pyramidal cells revealed a significantly stronger relationship among local (<140 <mu>m) pyramidal neurons compared with distant (>300 mum) neurons during non-theta-associated immobility and sleep but not during theta-associated running and walking. In contrast, cross-correlation between local pyramidal cell-interneuron pairs was significantly stronger than between distant pairs during theta oscillations but were similar during non-theta-associated behaviors. We suggest that network state-dependent functional clustering of neuronal activity emerges because of the differential contribution of the main excitatory inputs, the perforant path, and Schaffer collaterals during theta and non-theta behaviors.}, author = {Hirase, Hajima and Leinekugel, Xavier and Csicsvari, Jozsef L and Czurkó, András and Buzsáki, György}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {10}, publisher = {Society for Neuroscience}, title = {{Behavior-dependent states of the hippocampal network affect functional clustering of neurons}}, doi = {10.1523/JNEUROSCI.21-10-j0003.2001}, volume = {21}, year = {2001}, } @article{3540, abstract = {What determines the firing rate of cortical neurons in the absence of external sensory input or motor behavior, such as during sleep? Hero we report that, in a familiar environment, the discharge frequency of simultaneously recorded individual CA1 pyramidal neurons and the coactivation of cell pairs remain highly correlated across sleep-wake-steep sequences. However, both measures were affected when new sets of neurons were activated in a novel environment. Nevertheless, the grand mean firing rate of the whole pyramidal cell population remained constant across behavioral states and testing conditions. The findings suggest that long-term firing patterns of single cells can be modified by experience. We hypothesize that increased firing rates of recently used neurons are associated with a concomitant decrease in the discharge activity of the remaining population, leaving the mean excitability of the hippocampal network unaltered.}, author = {Hirase, Hajima and Leinekugel, Xavier and Czurkó, András and Csicsvari, Jozsef L and Buzsáki, György}, issn = {0027-8424}, journal = {PNAS}, number = {16}, pages = {9386 -- 9390}, publisher = {National Academy of Sciences}, title = {{Firing rates of hippocampal neurons are preserved during subsequent sleep episodes and modified by novel awake experience}}, doi = {10.1073/pnas.161274398}, volume = {98}, year = {2001}, } @article{3494, abstract = {Mutual synaptic interactions between GABAergic interneurons are thought to be of critical importance for the generation of network oscillations and for temporal encoding of information in the hippocampus. However, the functional properties of synaptic transmission between hippocampal interneurons are largely unknown. We have made paired recordings from basket cells (BCs) in the dentate gyrus of rat hippocampal slices, followed by correlated light and electron microscopical analysis. Unitary GABAAreceptor-mediated IPSCs at BC–BC synapses recorded at the soma showed a fast rise and decay, with a mean decay time constant of 2.5 ± 0.2 msec (32°C). Synaptic transmission at BC–BC synapses showed paired-pulse depression (PPD) (32 ± 5% for 10 msec interpulse intervals) and multiple-pulse depression during repetitive stimulation. Detailed passive cable model simulations based on somatodendritic morphology and localization of synaptic contacts further indicated that the conductance change at the postsynaptic site was even faster, decaying with a mean time constant of 1.8 ± 0.6 msec. Sequential triple recordings revealed that the decay time course of IPSCs at BC–BC synapses was approximately twofold faster than that at BC–granule cell synapses, whereas the extent of PPD was comparable. To examine the consequences of the fast postsynaptic conductance change for the generation of oscillatory activity, we developed a computational model of an interneuron network. The model showed robust oscillations at frequencies >60 Hz if the excitatory drive was sufficiently large. Thus the fast conductance change at interneuron–interneuron synapses may promote the generation of high-frequency oscillations observed in the dentate gyrusin vivo. }, author = {Bartos, Marlene and Vida, Imre and Frotscher, Michael and Geiger, Jörg and Jonas, Peter M}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {8}, pages = {2687 -- 2698}, publisher = {Society for Neuroscience}, title = {{Rapid signaling at inhibitory synapses in a dentate gyrus interneuron network.}}, doi = {10.1523/JNEUROSCI.21-08-02687.2001}, volume = {21}, year = {2001}, } @article{3496, abstract = {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 Ca2+ 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. }, author = {Alle, Henrik and Jonas, Peter M and Geiger, Jörg}, issn = {0027-8424}, journal = {PNAS}, number = {25}, pages = {14708 -- 14713}, publisher = {National Academy of Sciences}, title = {{PTP and LTP at a hippocampal mossy fiber-interneuron synapse}}, doi = {10.1073/pnas.251610898 }, volume = {98}, year = {2001}, } @article{3495, abstract = {High Ca2+ permeability and its control by voltage-dependent Mg2+ block are defining features of NMDA receptors. These features are lost if the principal NR1 subunit carries an asparagine (N) to arginine (R) substitution in a critical channel site at NR1 position 598. NR1(R) expression from a single allele in gene-targeted NR1+/R mice is lethal soon after birth, precluding analysis of altered synaptic functions later in life. We therefore employed the forebrain specific αCaMKII promoter to drive tTA-mediated tetracyclin sensitive transcription of transgenes for NR1(R) and for lacZ as reporter. Transgene expression was observed in cortex, striatum, hippocampus, amygdala and olfactory bulb and was mosaic in all these forebrain regions. It was highest in olfactory bulb granule cells, in most of which Ca2+ permeability and voltage-dependent Mg2+ block of NMDA receptors were reduced to different extents. This indicates significant impairment of NMDA receptor function by NR1(R) in presence of the wild-type NR1 complement. Indeed, even though NR1(R) mRNA constituted only 18% of the entire NR1 mRNA population in forebrain, the transgenic mice died during adolescence unless transgene expression was suppressed by doxycycline. Thus, glutamate receptor function can be altered in the mouse by regulated NR1(R) transgene expression.}, author = {Jerecic, Jasna and Schulze, Christian and Jonas, Peter M and Sprengel, Rolf and Seeburg, Peter and Bischofberger, Joseph}, issn = {0169-328X}, journal = {Molecular Brain Research}, number = {1-2}, pages = {96 -- 104}, publisher = {Elsevier}, title = {{Impaired NMDA receptor function in mouse olfactory bulb neurons by tetracycline-sensitive NR1 (N598R) expression}}, doi = {10.1016/S0169-328X(01)00221-2}, volume = {94}, year = {2001}, } @article{3517, abstract = {A modular multichannel microdrive ('hyperdrive') is described. The microdrive uses printed circuit board technology and flexible fused silica capillaries. The modular design allows for the fabrication of 4-32 independently movable electrodes or `tetrodes'. The drives are re-usable and re-loading the drive with electrodes is simple. }, author = {Szabo, Imre and Czurkó, András and Csicsvari, Jozsef L and Hirase, Hajima and Leinekugel, Xavier and Buzsáki, György}, issn = {0165-0270}, journal = {Journal of Neuroscience Methods}, number = {1}, pages = {105 -- 110}, publisher = {Elsevier}, title = {{The application of printed circuit board technology for fabrication of multi-channel micro-drives}}, doi = {10.1016/S0165-0270(00)00362-9}, volume = {105}, year = {2001}, } @article{3493, abstract = {Although agonists and competitive antagonists presumably occupy overlapping binding sites on ligand-gated channels, these interactions cannot be identical because agonists cause channel opening whereas antagonists do not. One explanation is that only agonist binding performs enough work on the receptor to cause the conformational changes that lead to gating. This idea is supported by agonist binding rates at GABAA and nicotinic acetylcholine receptors that are slower than expected for a diffusion-limited process, suggesting that agonist binding involves an energy-requiring event. This hypothesis predicts that competitive antagonist binding should require less activation energy than agonist binding. To test this idea, we developed a novel deconvolution-based method to compare binding and unbinding kinetics of GABAA receptor agonists and antagonists in outside-out patches from rat hippocampal neurons. Agonist and antagonist unbinding rates were steeply correlated with affinity. Unlike the agonists, three of the four antagonists tested had binding rates that were fast, independent of affinity, and could be accounted for by diffusion- and dehydration-limited processes. In contrast, agonist binding involved additional energy-requiring steps, consistent with the idea that channel gating is initiated by agonist-triggered movements within the ligand binding site. Antagonist binding does not appear to produce such movements, and may in fact prevent them.}, author = {Jones, M.V and Jonas, Peter M and Sahara, Y. and Westbrook, G.}, issn = {0006-3495}, journal = {Biophysical Journal}, number = {5}, pages = {2660 -- 2670}, publisher = {Biophysical Society}, title = {{Microscopic kinetics and energetics distinguish GABAA receptor agonists from antagonists}}, doi = {10.1016/S0006-3495(01)75909-7 }, volume = {81}, year = {2001}, } @article{2985, abstract = {The elimination voltammetry with linear scan (EVLS) was used to study adenine and cytosine reduction signals at the mercury electrode. In comparison with the linear scan voltammetry (which provides only one unresolved peak), two elimination functions provide good resolution of individual peaks and significant increase of sensitivity. The first elimination function eliminates the kinetic current (Ik) and conserves the diffusion current (Id). The second elimination function eliminates kinetic and charging currents (Ik and Ic) simultaneously and conserves the diffusion current (Id). Both functions give two well-resolved peaks of adenine and cytosine in a wide concentration range, while the linear sweep voltammetry gives badly resolved peaks due to hydrogen evolution. The best resolution of peaks is observed in acetate buffer at pH 3.8 and the detection limit for both substances is 500 nM. The concentration dependence of EVLS peak heights for one substance at the constant concentration of the other substance is linear. The peak potentials differ in these elimination functions. The difference in EVLS peak potentials gives the possibility to evaluate αna. Elimination voltammetry with linear scan contributes to the resolution of cathodic signals of purine and pyrimidine bases at very negative potentials near supporting electrolyte discharge. Copyright © 2001 Elsevier Science B.V.}, author = {Trnková, Libuše and Friml, Jirí and Dračka, Oldřich}, isbn = {1567-5394}, journal = {Bioelectrochemistry}, number = {2}, pages = {131 -- 136}, publisher = {Elsevier}, title = {{Elimination voltammetry of adenine and cytosine mixtures}}, doi = {10.1016/S1567-5394(01)00119-0}, volume = {54}, year = {2001}, }