Miniaturization of isothermal calorimeters provides an even wider range of possibilities.

The first isothermal calorimeter was devised and used in 1782–1783 by Lavoisier and Laplace to determine the heat produced during chemical changes. This was the ‘ice-calorimeter,’ in which a sufficient amount of ice was used to keep the temperature constant (Lavoisier & Laplace, 1780). These early scientists realized that the mass of liquid water produced by the melting ice was directly proportional to the heat selleck produced by the reaction taking place atop the ice. Many improvements have of course been made since the early 19th century. In addition, several other types of calorimeters have evolved besides the ones that operate isothermally – for example adiabatic, constant-volume, constant-pressure, heat loss and temperature (differential) scanning calorimeters (van Herwaarden, find more 2000). Some of them can also be used in the isothermal mode. In the isothermal approach, isothermal titration calorimetry has emerged as the broadly used standard for thermodynamic characterization of relatively fast reactions between molecules – for example ligand binding – especially for molecules of interest in biology (Cooper, 2003).

However, because isothermal titration calorimetry is mostly a tool for molecular studies, it is not covered here. This review focuses on IMC in microbiology for a wide variety of Acyl CoA dehydrogenase purposes including microorganism detection and discrimination, evaluation of microbial processes and determining the performance of antimicrobial agents. The term IMC is used here to refer to measurements in the microwatt range under essentially isothermal conditions (Wadsö, 2001). The related instruments are often called isothermal microcalorimeters. Most isothermal microcalorimeters are heat conduction calorimeters in which heat produced in the reaction vessel is allowed to flow to a heat sink, usually made of aluminum. Therefore,

so-called isothermal microcalorimeters are not truly isothermal, but allow small variations of the sample temperature (up to 0.1 °C). Variation in the sample temperature mostly does not affect the heat sink temperature significantly because the heat sink has a much higher heat capacity than the reaction vessel and its contents (usually × 100). In addition, the heat sink is often placed in a thermostat, ensuring its temperature stability. The heat transfer between the vessel and the heat sink takes place through a thermopile, allowing measurements of the heat produced or consumed (Wadsö & Goldberg, 2001). In other isothermal microcalorimeters, thermoelectric compensation is preferred to maintain isothermal conditions. Heat produced is compensated using Pelletier elements, and similarly, heat consumed is compensated either by an electric heater or by reversing the polarity of the Peltier elements (van Herwaarden, 2000).

Plain water was given to the controls at the same restricted time (R-Water). Clock gene Per2 expression was measured by a bioluminescence reporter in cultured brain tissues. In SCN-intact rats, Talazoparib solubility dmso MAO was induced by R-MAP and behavioral rhythms were phase-delayed from the restricted time under ad-MAP with relative coordination. Circadian Per2 rhythms in R-MAP rats were not affected in the SCN but were slightly phase-advanced in the

olfactory bulb (OB), caudate–putamen (CPU) and substantia nigra (SN) as compared with R-Water rats. Following SCN lesion, R-MAP-induced MAO phase-shifted more slowly and did not show a sign of relative coordination. In these rats, circadian Per2 rhythms were significantly phase-shifted in the OB and SN as compared with SCN-intact rats. These findings indicate that MAO was induced by MAP given at a restricted time of day in association with phase-shifts of the extra-SCN circadian oscillators in the brain dopaminergic areas. The findings also suggest that these extra-SCN oscillators are the components of MAO and receive dual regulation by MAO and the SCN circadian pacemaker. The circadian rhythms of physiology and behavior in mammals are controlled by a hierarchical multi-oscillator system, consisting

of a central circadian pacemaker in the suprachiasmatic nucleus (SCN) and peripheral oscillators in a variety of tissues and organs (Reppert & Weaver, 2002;

Mohawk et al., 2012). The SCN circadian pacemaker entrains to light–dark cycles (LD) and resets the peripheral oscillators. Intracellular Dabrafenib manufacturer Terminal deoxynucleotidyl transferase mechanisms of the central and peripheral circadian oscillators are considered to be an autoregulatory molecular feedback loop involving several clock genes and their protein products. On the other hand, at least two oscillators in the circadian range are reported to be induced independent of the SCN circadian pacemaker (Honma & Honma, 2009). One is the methamphetamine (MAP)-induced oscillator (MAO) and the other is the food-entrainable oscillator (FEO). MAO is induced by chronic MAP treatment via drinking water (Honma et al., 1986a; Tataroglu et al., 2006) and desynchronises some extra-SCN oscillators in the brain as well as behavioral rhythm from the SCN circadian pacemaker (Masubuchi et al., 2000; Natsubori et al., 2013b). The MAP-induced behavioral rhythms are regarded as an animal model of the human sleep–wake cycle because they show characteristics specifically observed in the human sleep–wake cycle such as internal desynchronisation, circabidian (ca. 48 h) rhythms and non-photic entrainment. On the other hand, FEO is induced by restricted daily feeding (RF) and characterised by anticipatory activity prior to daily meals (Stephan et al., 1979).

Plain water was given to the controls at the same restricted time (R-Water). Clock gene Per2 expression was measured by a bioluminescence reporter in cultured brain tissues. In SCN-intact rats, selleck chemical MAO was induced by R-MAP and behavioral rhythms were phase-delayed from the restricted time under ad-MAP with relative coordination. Circadian Per2 rhythms in R-MAP rats were not affected in the SCN but were slightly phase-advanced in the

olfactory bulb (OB), caudate–putamen (CPU) and substantia nigra (SN) as compared with R-Water rats. Following SCN lesion, R-MAP-induced MAO phase-shifted more slowly and did not show a sign of relative coordination. In these rats, circadian Per2 rhythms were significantly phase-shifted in the OB and SN as compared with SCN-intact rats. These findings indicate that MAO was induced by MAP given at a restricted time of day in association with phase-shifts of the extra-SCN circadian oscillators in the brain dopaminergic areas. The findings also suggest that these extra-SCN oscillators are the components of MAO and receive dual regulation by MAO and the SCN circadian pacemaker. The circadian rhythms of physiology and behavior in mammals are controlled by a hierarchical multi-oscillator system, consisting

of a central circadian pacemaker in the suprachiasmatic nucleus (SCN) and peripheral oscillators in a variety of tissues and organs (Reppert & Weaver, 2002;

Mohawk et al., 2012). The SCN circadian pacemaker entrains to light–dark cycles (LD) and resets the peripheral oscillators. Intracellular selleck screening library of mechanisms of the central and peripheral circadian oscillators are considered to be an autoregulatory molecular feedback loop involving several clock genes and their protein products. On the other hand, at least two oscillators in the circadian range are reported to be induced independent of the SCN circadian pacemaker (Honma & Honma, 2009). One is the methamphetamine (MAP)-induced oscillator (MAO) and the other is the food-entrainable oscillator (FEO). MAO is induced by chronic MAP treatment via drinking water (Honma et al., 1986a; Tataroglu et al., 2006) and desynchronises some extra-SCN oscillators in the brain as well as behavioral rhythm from the SCN circadian pacemaker (Masubuchi et al., 2000; Natsubori et al., 2013b). The MAP-induced behavioral rhythms are regarded as an animal model of the human sleep–wake cycle because they show characteristics specifically observed in the human sleep–wake cycle such as internal desynchronisation, circabidian (ca. 48 h) rhythms and non-photic entrainment. On the other hand, FEO is induced by restricted daily feeding (RF) and characterised by anticipatory activity prior to daily meals (Stephan et al., 1979).

A cross-sectional analysis was performed on 18 June 2011. Based on the last two values obtained in RT-PCR assays on that date, the patients were classified into three groups: strictly undetectable VL, i.e. the last two RT-PCR assays detecting no signal (group 1); detectable VL below the threshold, i.e. at least one RT-PCR assay detecting a signal < 20 copies/mL (group 2); and at least one RT-PCR assay measuring a VL of 20–50 copies/mL (group 3). Demographic data (age, sex and probable route of infection), therapeutic data (total duration

of cART, duration of current regimen, number of previous regimens, and duration of viral suppression < 50 copies/mL), and medical history (presence of an associated hepatitis infection, known duration of HIV infection, past AIDS-defining event, CD4 T-cell nadir, VL zenith (highest ever VL), and this website last CD4 T-cell count) were collected and compared between groups. All categorical data are described by frequencies and compared using χ2 tests. Continuous data are described by means (standard deviation) and compared using analysis of variance (ANOVA). Two multivariate analyses were performed. One analysed the characteristics of patients with strictly undetectable viral load (group 1) compared with those of patients with detectable Selleck Ibrutinib VL below the threshold of 20 copies/mL (group 2). The second analysed the characteristics

of patients with a strictly undetectable viral load (group 1) compared with those of patients with a VL of 20–50 copies/mL (group 3). All characteristics

with a P-value < 0.20 were then included in two multivariate logistic regressions comparing group 2 with group 1 and group 3 with group 1. Tests < 0.05 were considered statistically significant. All analyses were performed using sas version 9 (SAS Institute, Cary, NC). Of note, VL values < 20 copies/mL with or without PRKACG signal were reported to the clinic until the date of analysis as being below the threshold of 20 copies/mL, preventing any modification of the cART regimen. The study population included 1392 patients, with a mean age of 48 ± 10 years, of whom 69% were men. The mean time since HIV diagnosis was 14 ± 7 years and 20% had a past AIDS-defining event (stage C). The mean CD4 T-cell count nadir and VL zenith were, respectively, 225 ± 169 cells/μL and 4.6 ± 1.4 log10 copies/mL. The VL zenith was > 5 log10 copies/mL in 46% of the patients. The current mean CD4 T-cell count was 675 ± 333 cells/μL. The mean duration of viral suppression was 50 ± 36 months. The mean total duration of cART was 10 ± 5 years, with a mean number of previous anti-retroviral regimens of 5 ± 3. The current cART regimen was based on two nucleoside reverse transcriptase inhibitors (NRTIs) plus one bPI or one NNRTI or raltegravir in, respectively, 43, 45 and 12% of patients. The mean total duration of the current cART regimen was 35 ± 23 months.

The 12 most extreme cases, with only 0–4 HMM detections over 1051–1808 bp, were all identified as taxonomic misclassifications and represented eukaryotic 18S rather than bacterial or archaeal 16S sequences. This prevented detection by the domain-specific HMMs, although some HMMs that were designed at highly conserved regions were able to perform detections across taxonomic domains. Among the 92 less extreme cases, with 6 to 9 HMM detections over 900–1504 bp, most sequences (i.e. 75 cases) contained a sequence segment at either the 5′ or

the 3′ end that did not match any entry in GenBank, as assessed through blast. We extracted these segments from 15 entries and subjected them to a separate blast analysis. In 11 cases, the segment alone showed no reasonable match to any entry in GenBank, indicating that the segment probably represents erroneous sequence information. Linsitinib In the other four cases, the segment matched entries other than the matches from the full blast search, indicating that the entire sequence is probably chimeric. Eight sequences were chimeric, which might have reduced the number of HMM detections per read length equivalent. It is noteworthy in this case that most cases (76 out of 92) were click here flagged as being potentially chimeric in the SILVA database (average SILVA pintail score of 1.7%). In conclusion, the software showed extremely high detection reliability and flagged sequences

containing anomalies that can be detected by the algorithm such as reverse complementary chimeras or non-16S sequence information. Automated detection of the sequence

orientation might be particularly useful for environmental sequence data sets generated by high-throughput sequencing (HTS) techniques. However, the reduced length might affect detection reliability and speed could be a limiting factor in processing millions of reads in a reasonable time. In order to assess the performance of v-revcomp on HTS data, we extracted 332 835 and 13 876 V1-V2 subregions as well as 332 799 and 13 870 V1-V3 Mirabegron subregions from the bacterial and archaeal SILVA datasets using v-xtractor 2.0 (Hartmann et al., 2010). These two datasets simulate sequence lengths approximately equivalent to lengths generated by the current HTS platforms (V1-V2, 261±18 bp) and lengths that will likely be reached by the next-generation of HTS platforms (V1-V3, 481±22 bp). The bacterial V1-V2 and V1-V3 datasets were processed in 18 and 37 min, respectively, whereas both archaeal datasets took around 1 min. All sequences were given in the correct orientation, but five V1-V3 or four V1-V2 were flagged as containing one reverse complementary HMM detection. These were cases already flagged in the full-length dataset. In conclusion, the tool performed well also for the short sequence reads characteristic of HTS datasets. The processing time increases linearly with the number of sequences and the million reads obtained from a full round of 454 pyrosequencing is processed in around one hour.

The spectral width in the carbon dimension was 170 p.p.m. and 180 p.p.m., respectively. All spectra were processed and analyzed using Bruker’s topspin

(v3.0) software. Usually, zero-filling was applied to double the number of real points in each dimension. Chemical shifts were referenced to the HDO resonance at 4.7 p.p.m. Chemical shift assignments for 13C were determined indirectly from HSQC and HMBC spectra. Pseudomonas sp. strain Chol1 was subjected to random transposon mutagenesis Tofacitinib clinical trial by insertion of the transposon mini-Tn5 Km1 and screened for transposon mutants showing altered growth with cholate as described previously (Birkenmaier et al., 2007). One mutant, strain G12, was analyzed further. Strain G12 could not grow with cholate as the sole substrate, but it could grow with succinate in the presence of cholate. HPLC analysis of supernatants from these cultures revealed that strain G12 did not transform cholate at all. We then checked selleck compound whether strain G12 could grow with intermediates of cholate degradation. With supernatants containing DHADD (VIII), strain G12 could grow after a long lag phase. Notably, cells of strain G12 induced for growth with DHADD were also induced for cholate transformation during growth with succinate in

the presence of cholate. HPLC analysis revealed that cholate was transformed into several compounds with an absorption maximum at 244 nm, which is indicative of steroids with a 3-keto-1,4-diene structure of the A-ring (Philipp et al., 2006). In the next step, we identified the gene in strain G12, in which the mini-Tn5 Km1 had been inserted. The transposon Histone demethylase was inserted into an

ORF of 1212 bp at bp 333. The predicted protein had 403 amino acids and showed high identity to nonspecific lipid transfer proteins from various bacteria. Among these were two bacteria, for which growth with cholate had been demonstrated, namely Pseudoalteromonas haloplanktis strain TAC125 (Birkenmaier et al., 2007) and Comamonas testosteroni strain KF-1 (Rösch et al., 2008). The nonspecific lipid transfer proteins from strains TAC125 and KF-1 showed 80% and 68% identity, respectively, to the gene product from strain Chol1 (Fig. 2). This gene was named skt (for steroid β-ketothiolase) for reasons that will be described below. To investigate the function of skt for cholate degradation further, we decided to construct a defined mutant of this gene by subjecting strain Chol1 to insertional mutagenesis with the suicide vector pKnockoutG. The resulting strain Chol1-KO[skt] could not grow with cholate; growth with cholate was restored when an intact copy of skt was provided in trans on the vector pBBR1MCS-5 (Fig. 3a). This complementation clearly showed that the phenotype of this mutant was caused by the inactivation of skt. Strain Chol1-KO[skt] could grow with succinate in the presence of cholate (Fig. 3b).

The sequence of the amplicon was obtained by primer walking, starting with the original forward and reverse primers, and subsequently using the ends of the sequenced strands to design new primers in order to obtain contiguous sequence data (GenBank accession number GQ889493). The sequence revealed the

expected bacABCDE genes and showed 95% and 98% homology with the bac genes from B. subtilis A1/3 and B. amyloliquefaciens, respectively. No gene that might code for a halogenating GPCR Compound Library cell line enzyme was present within the cluster. Flanking regions were also sequenced, revealing a sequence coding for a possible penicillin-binding protein adjacent to bacA and a gene coding for an amino acid permease downstream from bacE, but no gene coding for a putative halogenase. Thus, Bacillus sp. CS93 has the necessary genes for bacilysin biosynthesis, but they did not seem to be expressed under the conditions that were used here. The mechanism of halogenation is still unclear, and if a halogenase is involved, the corresponding gene is at a different locus

on the chromosome. Selumetinib supplier It is also possible that the appearance of chlorotetaine in the culture supernatant is a consequence of an abiotic reaction between chloride ions and bacilysin. The presence of antibacterial activity in Bacillus sp. CS93 culture supernatants could not be accounted for by the production of iturin A (Peypoux et al., 1979) nor attributed to bacilysin/chlorotetaine, which suggested that the strain produced one or more other antibiotics that had not been identified in the original study (Phister et al., 2004). It was previously demonstrated that the activity in Bacillus sp. CS93 culture supernatants was inactivated in the presence of pronase E (Ray et al., 2000), indicating

that other peptide antibiotics might be produced by the strain. Using a degenerated primer based on the LGG conserved region in subdomain A10 of nonribosomal peptide synthases (Turgay & Marahiel, 1994) and a forward degenerated primer designed on the conserved region of the GTTG sequence motif in core subdomain A3 (Fig. 2), a 1.2-kb fragment was amplified from Methamphetamine Bacillus sp. CS93 genomic DNA. This was subsequently cloned into E. coli XL1-Blue; 25 positive clones were identified via blue/white screening, and of these, 21 were shown to have the 1.2-kb insert after digestion of the plasmid with EcoR1. These were sequenced and homology searches revealed that plasmid inserts YT 1-19 (GenBank accession number GU013559) had a 99% deduced amino acid sequence identity with surfactin synthetase (SrfAA) from B. amyloliquefaciens FZB42. Furthermore, plasmid inserts YT 20 and 21 (GenBank accession number GU013558) most closely matched the fengycin synthase (FenD) from the same species (99% amino acid sequence identity). Therefore, culture supernatants of the bacterium were examined for the presence of a surfactin and fengycin, after acidification and extraction of the precipitate with methanol.

The sequence of the amplicon was obtained by primer walking, starting with the original forward and reverse primers, and subsequently using the ends of the sequenced strands to design new primers in order to obtain contiguous sequence data (GenBank accession number GQ889493). The sequence revealed the

expected bacABCDE genes and showed 95% and 98% homology with the bac genes from B. subtilis A1/3 and B. amyloliquefaciens, respectively. No gene that might code for a halogenating Epacadostat enzyme was present within the cluster. Flanking regions were also sequenced, revealing a sequence coding for a possible penicillin-binding protein adjacent to bacA and a gene coding for an amino acid permease downstream from bacE, but no gene coding for a putative halogenase. Thus, Bacillus sp. CS93 has the necessary genes for bacilysin biosynthesis, but they did not seem to be expressed under the conditions that were used here. The mechanism of halogenation is still unclear, and if a halogenase is involved, the corresponding gene is at a different locus

on the chromosome. selleck screening library It is also possible that the appearance of chlorotetaine in the culture supernatant is a consequence of an abiotic reaction between chloride ions and bacilysin. The presence of antibacterial activity in Bacillus sp. CS93 culture supernatants could not be accounted for by the production of iturin A (Peypoux et al., 1979) nor attributed to bacilysin/chlorotetaine, which suggested that the strain produced one or more other antibiotics that had not been identified in the original study (Phister et al., 2004). It was previously demonstrated that the activity in Bacillus sp. CS93 culture supernatants was inactivated in the presence of pronase E (Ray et al., 2000), indicating

that other peptide antibiotics might be produced by the strain. Using a degenerated primer based on the LGG conserved region in subdomain A10 of nonribosomal peptide synthases (Turgay & Marahiel, 1994) and a forward degenerated primer designed on the conserved region of the GTTG sequence motif in core subdomain A3 (Fig. 2), a 1.2-kb fragment was amplified from Ureohydrolase Bacillus sp. CS93 genomic DNA. This was subsequently cloned into E. coli XL1-Blue; 25 positive clones were identified via blue/white screening, and of these, 21 were shown to have the 1.2-kb insert after digestion of the plasmid with EcoR1. These were sequenced and homology searches revealed that plasmid inserts YT 1-19 (GenBank accession number GU013559) had a 99% deduced amino acid sequence identity with surfactin synthetase (SrfAA) from B. amyloliquefaciens FZB42. Furthermore, plasmid inserts YT 20 and 21 (GenBank accession number GU013558) most closely matched the fengycin synthase (FenD) from the same species (99% amino acid sequence identity). Therefore, culture supernatants of the bacterium were examined for the presence of a surfactin and fengycin, after acidification and extraction of the precipitate with methanol.

The micropipette was held in place for 5 min after injection and then withdrawn slowly

to minimise backflow. The skin was resealed with Vetbond and sutures. Animals were given buprenorphine for analgesia prior to awakening, and were maintained on carprofen-containing chow (Rimadyl chewies, BioServ) for 3 days postsurgery. Mice were killed by carbon dioxide inhalation at 3–4 weeks or 12 months postinjection. Brains were fixed overnight at 4 °C in fresh 4% paraformaldehyde and then transferred to 30% sucrose for cryoprotection. Brains were frozen on dry ice and then sectioned selleck products at 45 μm using a freezing-sliding microtome. Sections were stored in antifreeze buffer [50 mm NaPO4, pH 7.4, containing 25% glycerol and 30% ethylene glycol (v/v)] at −20 °C until use. Brain sections of mice injected with AAV-YFP at P0 or P3 were immunostained with neuronal nuclei (NeuN), Ca2+/calmodulin-dependent protein kinase II α, S 100 calcium binding protein B (S100β), ionised calcium binding adaptor molecule 1, glutamate decarboxylase 67 (GAD67), calbindin D-28k or β-galactosidase (β-gal) antibodies to determine the phenotype of YFP-positive cells. Sections were washed with Tris-buffered saline to remove antifreeze medium,

followed by permeabilisation and blocking with 3% goat serum plus 0.1% Triton-X 100 in Tris-buffered saline for 1 h at room temperature. Sections were then incubated with mouse anti-S100β (1 : 500; Sigma, S2632), rabbit anti-ionised calcium binding adaptor molecule 1(1 μg/mL; Wako Chemicals, 019-19741), mouse anti-NeuN (1 : 1000; Millipore, MAB377), mouse Selleckchem Androgen Receptor Antagonist anti-Ca2+/calmodulin-dependent protein kinase IIα (1 : 1000, Chemicon, MAB3119), rabbit anti-GAD67 (1 : 1000; Chemicon, AB5992), mouse anti-calbindin D-28k

(1 : 5000, Swant, McAB 300) or chicken anti-β-gal antibody (1 : 5000, Abcam, ab9361) in blocking solution at 4 °C overnight. The following day the sections were washed with Tris-buffered saline and incubated for 2 h at room temperature with Alexa Fluor 594-conjugated goat anti-rabbit (1 : 500; Invitrogen, A11012), Alexa Fluor 568-conjugated donkey anti-mouse (1 : 500; Invitrogen, A10037), or Alexa Fluor 647-conjugated goat anti-chicken (1 : 500, Invitrogen, A21449) secondary antibody for fluorescent detection. Edoxaban The 4- and 8-week-old P0-injected mice were anesthetised with isoflurane, and a 3 mm cranial window was placed as described in previous studies (Holtmaat et al., 2009). For imaging of cortical pyramidal neurons, the window was centered at 2 mm lateral and 2 mm posterior to the bregma. For imaging of cerebellar Purkinje cells, the window was centered at 1.5 mm lateral and 2 mm posterior to the lambda. Following 2–5 days of recovery, in vivo images were acquired using a Prairie View two-photon microscope. A Coherent Ti:Sapphire laser tuned to 890 nm was focused into tissue using a 20 × (0.95 NA) or 60 × (1.0 NA) Olympus lens at 10–40 mW (0.

“
“Early visual areas (V1, V2, V3/VP, V4v) contain representations of the contralateral hemifield within each hemisphere. Little is known about the role of the visual hemifields along the visuo-spatial attention processing hierarchy. It is hypothesized that attentional information processing is more efficient across the hemifields (known as bilateral field advantage) and that the integration of information is greater within one hemifield as compared with across the hemifields.

Using functional magnetic resonance imaging we examined the effect of distance and hemifield on parallel attentional processing in the early visual areas (V1–V4v) at individually mapped retinotopic locations aligned adjacently or separately within or across the hemifields. We found XL184 that the bilateral field advantage in parallel attentional processing over separated attended locations can be assigned, at least partly, to differences in distractor

position integration in early visual areas. These results provide evidence for a greater integration of locations between two attended locations within one hemifield than across both hemifields. This nicely correlates with behavioral findings of a bilateral field advantage in parallel attentional processing (when distractors in between cannot be excluded) and MAPK inhibitor a unilateral field advantage if attention has to be shifted across separated locations (when locations in between were integrated). “
“The speed of computations in neocortical networks Oxymatrine critically depends on the ability of populations of spiking neurons to rapidly detect subtle changes in the input and translate them into firing rate changes. However, high sensitivity to perturbations may lead to explosion of noise and increased energy consumption. Can neuronal networks reconcile the requirements for high

sensitivity, operation in a low-noise regime, and constrained energy consumption? Using intracellular recordings in slices from the rat visual cortex, we show that layer 2/3 pyramidal neurons are highly sensitive to minor input perturbations. They can change their population firing rate in response to small artificial excitatory postsynaptic currents (aEPSCs) immersed in fluctuating noise very quickly, within 2–2.5 ms. These quick responses were mediated by the generation of new, additional action potentials (APs), but also by shifting spikes into the response peak. In that latter case, the spike count increase during the peak and the decrease after the peak cancelled each other, thus producing quick responses without increases in total spike count and associated energy costs. The contribution of spikes from one or the other source depended on the aEPSCs timing relative to the waves of depolarization produced by ongoing activity.