Increased Response Latencies Research Articles

Therapeutic potential of andrographolide for treating endometriosis

Mounting evidence shows that nuclear factor-κB (NF-κB) plays an important role in endometriosis. We therefore evaluated the therapeutic potential of andrographolide, an NF-κB inhibitor. Primary cell cultures were performed using ectopic endometrial tissue specimens and their homologous eutopic endometrial specimens from 16 women with endometriosis, as well as control samples from 4 women without endometriosis. Andrographolide was evaluated for an effect on cell proliferation and cell cycle, DNA-binding activity of NF-κB and expression of cyclooxygenase-2 (COX-2) and tissue factor (TF). In a rat model of endometriosis, andrographolide treatment was evaluated for an effect on lesion size, hotplate response latency and expression of phosphorylated p50 and p65, COX-2 and nerve growth factor (NGF) in ectopic endometrium. Andrographolide dose dependently suppressed proliferation and cell cycle progression, attenuated DNA-binding activity of NF-κB in endometriotic stromal cells and inhibited COX-2 and TF expression. In the rat experiment, induced endometriosis resulted in reduced response latency. Andrographolide treatment significantly reduced lesion size in a dose-dependent manner and significantly increased response latency. Andrographolide treatment also significantly reduced immunoreactivity of COX-2, phosphorylated p50 and p65, and NGF in ectopic endometrium. Treatment with andrographolide significantly suppresses the growth of ectopic endometrium in vitro and in vivo, and results in a significant improvement in generalized hyperalgesia in rats with induced endometriosis. Therefore, andrographolide may be cytoreductive and may relieve pain symptoms in women with endometriosis. With excellent safety and cost profiles, andrographolide could be a promising therapeutic agent for endometriosis.

Once bitten twice shy: long‐term behavioural changes caused by trapping experience in willow warblersPhylloscopus trochilus

In dangerous situations, animals learn from experience to anticipate risks during similar subsequent occasions. Mist netting may represent just such a dangerous occasion and may serve as a tool to get insight into whether and how memorizing and recognition of the circumstances that form the prelude to a recapture can alter the animal's behaviour after capture, as well as it may affect the subsequent recapture rates. We used a playback lure to study the capture latency in willow warblersPhylloscopus trochilus, both without any and with a previous capture experience (either in the same year or in a previous one). We found increased response latencies to the playback lure for experienced males, compared to naive males. Naive males responded faster in the presence of a mist net than without a mist net; while experienced males tended to increase their response latencies. Individuals with between‐year capture experience showed exactly the same response pattern as individuals with a capture experience within the same year. These findings suggest that the birds may recall the capture event even a year later. It is very likely that the playback lure, with or without the net's presence, contributed significantly to the apparent risk of detection. We believe our study reveals that long‐lasting modifications of behaviour induced by capture and handling deserve further attention, as they might have a serious impact on the value of behavioural and ecological data, which is either based upon observing captured individuals and/or upon the recapture rates.

The Effect of Music‐Induced Mood on Aggressive Affect, Cognition, and Behavior1

Two studies explored the role of pleasant music in buffering the adverse effects of provocation. In the first study, 111 participants listened to aversive, pleasant, or no music before receiving a provocation and completing a measure of aggressive behavior. Participants exposed to pleasant music reported more positive mood. Those in the aversive music condition reported more negative mood than did those in the no‐music control condition. The more positive the music‐induced mood, the less anger was experienced and aggressive behavior was shown after provocation. In Study 2 (N = 142), listening to pleasant music reduced anger following provocation, compared to aversive music and a no‐music control condition. Pleasant music also increased response latencies in recognizing aggressive words after provocation.

Effects of Prazosin, an α1‐Adrenergic Receptor Antagonist, on the Seeking and Intake of Alcohol and Sucrose in Alcohol‐Preferring (P) Rats

Previous studies show that prazosin, an α(1) -adrenergic receptor antagonist, decreases alcohol drinking in animal models of alcohol use and dependence [Rasmussen et al. (2009) Alcohol Clin Exp Res 3:264-272; Walker et al. (2008) Alcohol 42:91-97] and in alcohol-dependent men [Simpson et al. (2009) Alcohol Clin Exp Res 33:255-263]. This study extended these findings by using a paradigm that allows for separate assessment of prazosin on motivation to seek versus consume alcohol or sucrose in selectively bred rats. Alcohol-preferring (P) rats were trained to complete an operant response that resulted in access to either 2% sucrose or 10% alcohol. A 4-week Seeking Test Phase examined responding in single, weekly extinction sessions when no reinforcer could be obtained. A 4-week Drinking Test Phase consisted of rats lever-pressing to "pay" a specified amount up front to gain access to unlimited alcohol (or sucrose) for a 20-minute period. On Seeking and Drinking test days, prazosin (0.0, 0.5, 1.0, and 1.5 mg/kg) was administered intraperitoneally 30 minutes prior to behavioral sessions. Rats were self-administering an average of 0.9 (±0.09) g/kg alcohol on vehicle test day and had pharmacologically relevant blood ethanol concentrations. Prazosin significantly decreased alcohol seeking at all doses tested. The highest dose of prazosin also increased the latency to first response for alcohol and decreased alcohol intake. While sucrose-seeking and intake were similarly affected by prazosin, the high dose of prazosin did not increase response latency. These findings are consistent with and extend previous research and suggest that prazosin decreases motivation to initiate and engage in alcohol consumption. The specificity of prazosin in attenuating the initiation of alcohol- but not sucrose-seeking suggests that this effect is not because of prazosin-induced motor-impairment or malaise. Together with previous findings, these data suggest that prazosin may be an effective pharmacotherapy, with specific application in people that drink excessively or have a genetic predisposition to alcohol abuse.

Inhibition of KCC2 in Mouse Spinal Cord Neurons Leads to Hypersensitivity to Thermal Stimulation

KCC2, a neuronal-specific K-Cl cotransporter, is involved in pain perception physiology through its effects on postsynaptic inhibition in spinal cord neurons. We injected a newly identified, highly potent and selective inhibitor of KCC2 (D4), an inactive structural variant (D4.14), and the Na-K-2Cl cotransporter (NKCC1) inhibitor, bumetanide, into the intrathecal space of mice to measure their effect on heat-evoked nociceptive responses. Commercially available intrathecal catheters were modified and surgically placed into 2 cohorts of 10 mice. After recovery from the procedure, the mice were injected with D4, D4.14, and bumetanide through this catheter. Nociceptive measurements (hotplate assay, tail flick assay) were performed after injection of each of the test drugs and compared with vehicle controls. Two mice in each cohort were omitted because of postprocedure complications. There was a statistically significant decrease (P < 0.01) in withdrawal latency after injection of the active KCC2 inhibitor but not after injection of the inactive compound (P = 0.78), as measured by hotplate assay at 55°C. Injection of bumetanide significantly increased withdrawal latency (P = 0.02) at the same temperature. These results were confirmed using tail flick assays performed at 49°C. Inhibition of KCC2 by D4 led to decreased heat-evoked withdrawal latency in mice, as measured by hotplate and tail flick assays, whereas inhibition of NKCC1 by bumetanide resulted in increased response latencies to heat stimuli as measured by both of these nociceptive tests.

Rapid Plasticity of Visual Responses in the Adult Lateral Geniculate Nucleus

Compared to the developing visual system, where neuronal plasticity has been well characterized at multiple levels, little is known about plasticity in the adult, particularly within subcortical structures. We made intraocular injections of 2-amino-4-phosphonobutyric acid (APB) in adult cats to block visual responses in On-center retinal ganglion cells and examined the consequences on visual responses in the lateral geniculate nucleus (LGN) of the thalamus. In contrast to current views of retinogeniculate organization, which hold that On-center LGN neurons should become silent with APB, we find that ∼50% of On-center neurons rapidly develop Off-center responses. The time course of these emergent responses and the actions of APB in the retina indicate the plasticity occurs within the LGN. These results suggest there is greater divergence of retinogeniculate connections than previously recognized and that functionally silent, nonspecific retinal inputs can serve as a substrate for rapid plasticity in the adult.

Amplitude and timing of somatosensory cortex activity in task-specific focal hand dystonia

Objective Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear. Methods In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from 13 patients and matched controls. Results Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength. Conclusions There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD. Significance Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning-based sensorimotor interventions.

Alogia and formal thought disorder: Differential patterns of verbal fluency task performance

BackgroundThere is evidence that alogia and formal thought disorder (FTD), two prominent speech symptoms in schizophrenia, are associated with different patterns of verbal fluency task deficits. Verbal fluency is thought to involve several cognitive mechanisms, including controlled retrieval, semantic memory, and context processing. MethodsThe current research examined whether alogia and FTD were associated with different patterns of verbal fluency performance and whether these patterns of verbal fluency performance would implicate deficits in controlled retrieval, semantic memory, or context processing. In the current research, 34 people with schizophrenia completed letter and category fluency tasks and detailed ratings of alogia and FTD symptoms were made from typed transcripts. ResultsOverall, alogia was associated with increased response latency between each word on the category fluency task, suggesting an association between alogia and poor controlled retrieval. In contrast, FTD was associated with a decreased proportion of semantically-related words on letter fluency, suggesting an association between FTD and poor context processing. ConclusionsAlogia and FTD appear to be associated with unique patterns of fluency performance, implicating separate cognitive mechanisms.

Sexual Material Perception in Sexually Coercive Men: Disattending Deficit and Its Covariates

The perceptual bias for sexual material has been explored mainly in normal men, and to date little attention has been paid to sexually aggressive men. The current study compared performance of sexually aggressive and nonaggressive men on experimental tasks involving sexual stimuli. Participants viewed the visual images (neutral or sexual), and, depending on the cue they were presented, they either responded to shape and color questions or just skipped to the next trial. In contrast with noncoercive men, men who admitted sexually coercive behavior showed increased response latencies only in the condition in which they were required to withdraw their attention from sexual stimuli to perform the cognitive task. Correlations with attentional performance suggested that sexually coercive men high on impulsivity and aggressiveness might experience cognitive interference when processing sexual material. These results are interpreted using disinhibition and response modulation models.

Effects of morphine on pain-elicited and pain-suppressed behavior in CB1 knockout and wildtype mice

Pharmacological manipulations of the type 1 cannabinoid receptor (CB1) suggest a role for CB1 in morphine-induced antinociception, but studies utilizing CB1 knockout (KO) mice do not support this conclusion. Since studies using CB1 KO mice to study morphine's antinociceptive effects have only examined thermal nociception, this study examines these interactions in models that employ a chemical stimulus. To determine whether the findings obtained with thermal pain models extend to other models, the effects of morphine on acetic acid-induced writhing were examined in CB1 KO and wildtype (WT) mice. Behaviors that decrease in response to acid injection, feeding and wheel running, were also examined, and investigations were carried out in the thermal hotplate assay. The CB1 antagonist SR141716A was also examined in these assays. Morphine completely blocked acid-induced writhing (1.0-10.0 mg/kg) and increased response latencies in the hotplate (10.0-32.0 mg/kg) in both genotypes. Morphine (3.2 mg/kg) significantly attenuated the suppression of wheel running but did not completely prevent this effect in either genotype. Morphine did not alter pain-suppressed feeding. In each of these assays, morphine's effects were not altered in CB1 KO mice compared with WT mice; however, SR141716A attenuated morphine's effects in C57BL/6 mice. The effects of morphine do not differ in CB1 KO and WT mice in preclinical pain models using thermal and chemical stimuli. Since SR141716A did attenuate the effects of morphine, it is possible that CB1 KO mice undergo developmental changes that mask the role of CB1 receptors in morphine's antinociceptive effects.

Transcranial magnetic stimulation of medial prefrontal cortex modulates face expressions processing in a priming task

The medial prefrontal cortex (mPFC) and the right somatosensory cortex (rSC) are known to be involved in emotion processing and face expression recognition, although the possibility of segregated circuits for specific emotions in these regions remains unclear. To investigate this issue, we used transcranial magnetic stimulation (TMS) together with a priming paradigm to modulate the activation state of the mPFC and the rSC during emotional expressions discrimination. This novel paradigm allows analyzing how TMS interacts with the ongoing activity of different neuronal populations following prime processing. Participants were asked to discriminate between angry and happy faces that were preceded by a congruent prime (a word expressing the same emotion), an incongruent prime (a word expressing the opposite emotion) or a neutral prime. In TMS trials, a single pulse was delivered over the mPFC, rSC or Vertex (control site) between prime and target presentation. TMS applied over the mPFC significantly affected the priming effect, by selectively increasing response latencies in congruent trials. This indicates that the mPFC contains different neural representations for angry and happy expressions. TMS over rSC did not significantly affect the priming effect, suggesting that rSC is not involved in processing verbal emotional stimuli.

Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague–Dawley rats

Neuronal nicotinic receptor systems have been shown to play key roles in cognition. Nicotine and nicotinic analogs improve attention and nicotinic antagonists impair it. This study was conducted to investigate the role of α4β2 nicotinic receptors in sustained attention using a novel selective α4β2 nicotinic receptor ligand, sazetidine-A. Female rats were trained to perform the signal detection task to a stable baseline of accuracy. The rats were injected with saline, sazetidine-A (0.01, 0.03, and 0.1mg/kg), dizocilpine (0.05mg/kg), or their combination; or, in another experiment, the rats were injected with the same doses of sazetidine-A, scopolamine (0.02mg/kg), or their combination. Percent hit and percent correct rejection showed that dizocilpine caused significant (p < 0.025) impairments in performance, which were significantly reversed by each of the sazetidine-A doses. Response omissions were significantly (p < 0.05) increased by dizocilpine, and this was also significantly reversed by each of the sazetidine-A doses. None of the sazetidine-A doses had significant effects on hit, correct rejection, or response omissions when given alone. Scopolamine also caused significant (p < 0.0005) impairments in percent hit and percent correct rejection and increased response omissions, which were significantly attenuated by all the sazetidine-A doses for percent hit and response omissions and by the highest dose of sazetidine-A for percent correct rejection. Both scopolamine and dizocilpine significantly (p < 0.0005) increased response latency, an effect which was significantly attenuated by sazetidine-A coadministration. These studies imply an important role for α4β2 nicotinic receptors in improving sustained attention under conditions that disrupt it. Very low doses of sazetidine-A or drugs with a similar profile may provide therapeutic benefit for reversing attentional impairment in patients suffering from mental disorders and/or cognitive impairment.

Contributions of the nucleus accumbens and its subregions to different aspects of risk-based decision making

The nucleus accumbens (NAc) has been implicated in mediating different forms of decision making in humans and animals. In the present study, we observed that inactivation of the rat NAc, via infusion of GABA agonists, reduced preference for a large/risky option and increased response latencies on a probabilistic discounting task. Discrete inactivations of the NAc shell and core revealed further differences between these regions in mediating choice and response latencies, respectively. The effect on choice was attributable to reduced win-stay performance (i.e., choosing risky after a being rewarded for a risky choice on a preceding trial). Moreover, NAc inactivation altered choice only when the large/risky option had greater long-term value, in terms of the amount of food that could be obtained over multiple trials relative to the small/certain option. Inactivation of the NAc or the shell subregion also slightly reduced preference for larger rewards on a reward magnitude discrimination. Thus, the NAc seems to play a small role in biasing choice toward larger rewards, but its contribution to behavior is amplified when delivery of these rewards is uncertain, helping to direct response selection toward more favorable outcomes.

Effects of recent word exposure on emotion-word Stroop interference: An ERP study

Attentional bias towards emotional linguistic material has been examined extensively with the emotion-word Stroop task. Although findings in clinical groups show an interference effect of emotional words that relate to the specific concern of the group, findings concerning healthy groups are less clear. In the present study, we investigated whether emotional Stroop interference in healthy individuals is affected by exposure of the words prior to the task. We used event-related potentials (ERPs) to examine the temporal aspects of Stroop interference. Participants took longer to indicate the colour of negative than of neutral words. Exposure of words prior to the Stroop task increased response latencies, but this effect was equal for neutral and negative words. At the neurophysiological level, we found more positive-going ERPs at later latencies (P290, N400 and LPP) in response to negative than in response to neutral Stroop words. The N400 was less negative for exposed than for new words, but this effect did not interact with the emotional valence of the words. For new (i.e., unexposed) words, the behavioural Stroop interference correlated with the P290, N400 and LPP emotion effects (negative minus neutral words). The successive ERP components suggest better prelexical, semantic, and sustained attentional processing of emotion words, even when the emotional content of the words is task-irrelevant.

Role of distinct parietal areas in arithmetic: An fMRI-guided TMS study

Although several parietal areas are known to be involved in number processing, their possible role in arithmetic operations remains debated. It has been hypothesized that the horizontal segment of the intraparietal sulcus (hIPS) and the posterior superior parietal lobule (PSPL) contribute to operations solved by calculation procedures, such as subtraction, but whether these areas are also involved in operations solved by memory retrieval, such as multiplication, is controversial. In the present study, we first identified the parietal areas involved in subtraction and multiplication by means of functional magnetic resonance imaging (fMRI) and we found an increased activation, bilaterally, in the hIPS and PSPL during both arithmetic operations. In order to test whether these areas are causally involved in subtraction and multiplication, we used transcranial magnetic stimulation (TMS) to create, in each participant, a virtual lesion of either the hIPS or PSPL, over the sites corresponding to the peaks of activation gathered in fMRI. When compared to a control site, we found an increase in response latencies in both operations after a virtual lesion of either the left or right hIPS, but not of the PSPL. Moreover, TMS over the hIPS increased the error rate in the multiplication task. The present results indicate that even operations solved by memory retrieval, such as multiplication, rely on the hIPS. In contrast, the PSPL seems to underlie processes that are nonessential to solve basic subtraction and multiplication problems.

Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and d-amphetamine, but unaffected by the COMT inhibitor tolcapone

Prefrontal cortical dopamine (DA) and norepinephrine (NE) are implicated in multiple aspects of cognitive function assessed via the 5-choice serial reaction time task (5-CSRTT) in rodents. The present studies assessed the effects of the NE reuptake inhibitor atomoxetine (0.5–2.0 mg/kg), the mixed DA/NE reuptake inhibitor methylphenidate (0.1–2.0 mg/kg), the catecholamine releaser d-amphetamine (0.1–1.0 mg/kg) and the catecholamine-o-methyl-transferase (COMT) inhibitor tolcapone (3.0–30.0 mg/kg) in rats that exhibited sub-optimal performance (reduced accuracy: <70% correct) in the 5-CSRTT. Increased ITI durations were associated with increased premature responding. Decreased ITI durations resulted in increased percent omissions, increased perseverative responses and increased response latencies, but had no effects on magazine latencies or percent correct. Atomoxetine decreased premature responding at prolonged ITI durations and methylphenidate decreased percent omissions at low doses (0.1 and 0.5 mg/kg). By contrast, d-amphetamine increased premature and perseverative responding in a dose-dependent manner (0.3–1.0 mg/kg). Finally, tolcapone had no effects on sub-optimal performance in the variable ITI 5-CSRTT. These results suggest minimal potential of tolcapone as a therapeutic agent for ADHD and implicate cortical NE, not DA, in impulsive action.

Tuberoinfundibular peptide of 39 residues (TIP39) signaling modulates acute and tonic nociception

Tuberoinfundibular peptide of 39 residues (TIP39) synthesizing neurons at the caudal border of the thalamus and in the lateral pons project to areas rich in its receptor, the parathyroid hormone 2 receptor (PTH2R). These areas include many involved in processing nociceptive information. Here we examined the potential role of TIP39 signaling in nociception using a PTH2R antagonist (HYWH) and mice with deletion of TIP39's coding sequence or PTH2R null mutation. Intracerebroventricular (icv) infusion of HYWH significantly inhibited nociceptive responses in tail-flick and hot-plate tests and attenuated the nociceptive response to hindpaw formalin injection. TIP39-KO and PTH2R-KO had increased response latency in the 55 °C hot-plate test and reduced responses in the hindpaw formalin test. The tail-flick test was not affected in either KO line. Thermal hypoalgesia in KO mice was dose-dependently reversed by systemic administration of the cannabinoid receptor 1 (CB1) antagonist rimonabant, which did not affect nociception in wild-type (WT). Systemic administration of the cannabinoid agonist CP 55,940 did not affect nociception in KO mice at a dose effective in WT. WT mice administered HYWH icv, and both KOs, had significantly increased stress-induced analgesia (SIA). Rimonabant blocked the increased SIA in TIP39-KO, PTH2R-KO or after HYWH infusion. CB1 and FAAH mRNA were decreased and increased, respectively, in the basolateral amygdala of TIP39-KO mice. These data suggest that TIP39 signaling modulates nociception, very likely by inhibiting endocannabinoid circuitry at a supraspinal level. We infer a new central mechanism for endocannabinoid regulation, via TIP39 acting on the PTH2R in discrete brain regions.

Spatio-temporal brain dynamics in a combined stimulus–stimulus and stimulus–response conflict task

It is yet not well known whether different types of conflicts share common or rely on distinct brain mechanisms of conflict processing. We used a combined Flanker (stimulus–stimulus; S–S) and Simon (stimulus–response; S–R) conflict paradigm both in an fMRI and an EEG study. S–S conflicts induced stronger behavioral interference effects compared to S–R conflicts and the latter decayed with increasing response latencies. Besides some similar medial frontal activity across all conflict trials, which was, however, not statically consistent across trials, we especially found distinct activations depending on the type of conflict. S–S conflicts activated the anterior cingulate cortex and modulated the N2 and early P3 component with underlying source activity in inferior frontal cortex. S–R conflicts produced distinct activations in the posterior cingulate cortex and modulated the late P3b component with underlying source activity in superior parietal cortex. Double conflict trials containing both S–S and S–R conflicts revealed, first, distinct anterior frontal activity representing a meta-processing unit and, second, a sequential modulation of the N2 and the P3b component. The N2 modulation during double conflict trials was accompanied by increased source activity in the medial frontal gyrus (MeFG). In summary, S–S and S–R conflict processing mostly rely on distinct mechanisms of conflict processing and these conflicts differentially modulate the temporal stages of stimulus processing.

Neural mechanisms of target ranging in FM bats: physiological evidence from bats and frogs

Echolocating bats assess target range by the delay in echo relative to the emitted sonar pulse. Earlier studies in FM bats showed that a population of neurons in auditory centers above the inferior colliculus (IC) is tuned to echo delay, with different neurons tuned to different echo delays. A building block for delay-tuned responses is paradoxical latency shift (PLS), featuring longer response latencies to more intense sounds. PLS is first created in the IC, where neurons exhibit unit-specific quantum increase in response latency with increasing sound level. Other IC neurons display oscillatory discharges whose period is unit-specific and level tolerant, indicating that this is attributable to cell's intrinsic properties. High-threshold inhibition of oscillatory discharge produces PLS, indicating that oscillatory discharge is a building block for PLS. To investigate the cellular basis of oscillatory discharges, we performed whole-cell patch-clamp recordings from IC neurons in leopard frogs (which also exhibit oscillatory discharges and PLS). These recordings show that IC neurons are heterogeneous displaying diverse biophysical phenotypes; each phenotype (and cell) has its own membrane time constant, input resistance, and strengths of I(h), I(kir), I(kv)--these intrinsic properties give rise to cell-specific resonance which can be observed through current and afferent stimulations.

Response Latency to Lingual Taste Stimulation Distinguishes Neuron Types Within the Geniculate Ganglion

The purpose of this study was to investigate the role of response latency in discrimination of chemical stimuli by geniculate ganglion neurons in the rat. Accordingly, we recorded single-cell 5-s responses from geniculate ganglion neurons (n = 47) simultaneously with stimulus-evoked summated potentials (electrogustogram; EGG) from the anterior tongue to signal when the stimulus contacted the lingual epithelium. Artificial saliva served as the rinse solution and solvent for all stimuli [(0.5 M sucrose, 0.03-0.5 M NaCl, 0.01 M citric acid, and 0.02 M quinine hydrochloride (QHCl)], 0.1 M KCl as well as for 0.1 M NaCl +1 μM benzamil. Cluster analysis separated neurons into four groups (sucrose specialists, NaCl specialists, NaCl/QHCl generalists and acid generalists). Artificial saliva elevated spontaneous firing rate and response frequency of all neurons. As a rule, geniculate ganglion neurons responded with the highest frequency and shortest latency to their best stimulus with acid generalist the only exception. For specialist neurons and NaCl/QHCl generalists, the average response latency to the best stimulus was two to four times shorter than the latency to secondary stimuli. For NaCl-specialist neurons, response frequency increased and response latency decreased systematically with increasing NaCl concentration; benzamil significantly decreased NaCl response frequency and increased response latency. Acid-generalist neurons had the highest spontaneous firing rate and were the only group that responded consistently to citric acid and KCl. For many acid generalists, a citric-acid-evoked inhibition preceded robust excitation. We conclude that response latency may be an informative coding signal for peripheral chemosensory neurons.