Sampling Time and Performance in Rat Whisker Sensory System

We designed a behavioural paradigm for vibro-tactile detection to characterise the sampling time and performance in the rat whisker sensory system. Rats initiated a trial by nose-poking into an aperture where their whiskers came into contact with two meshes. A continuous nose-poke for a random duration triggered stimulus presentation. Stimuli were a sequence of discrete Gaussian deflections of the mesh that increased in amplitude over time – across 5 conditions, time to maximum amplitude varied from 0.5 to 8 seconds. Rats indicated the detected stimulus by choosing between two reward spouts. Two rats completed more than 500 trials per condition. Rats'' stimulus sampling duration increased and performance dropped with increasing task difficulty. For all conditions the median reaction time was longer for correct trials than incorrect trials. Higher rates of increment in stimulus amplitude resulted in faster rise in performance as a function of stimulus sampling duration. Rats'' behaviour indicated a dynamic stimulus sampling whereby nose-poke was maintained until a stimulus was correctly identified or the rat experienced a false alarm. The perception was then manifested in behaviour after a motor delay. We thus modelled the results with 3 parameters: signal detection, false alarm, and motor delay. The model captured the main features of the data and produced parameter estimates that were biologically plausible and highly similar across the two rats.     

Discrimination of Auditory Stimuli during Isoflurane Anesthesia

Deep isoflurane anesthesia initiates a burst suppression pattern in which high-amplitude bursts are preceded by periods of nearly silent electroencephalogram. The burst suppression ratio (BSR) is the percentage of suppression (silent electroencephalogram) during the burst suppression pattern and is one parameter used to assess anesthesia depth. We investigated cortical burst activity in rats in response to different auditory stimuli presented during the burst suppression state. We noted a rapid appearance of bursts and a significant decrease in the BSR during stimulation. The BSR changes were distinctive for the different stimuli applied, and the BSR decreased significantly more when stimulated with a voice familiar to the rat as compared with an unfamiliar voice. These results show that the cortex can show differential sensory responses during deep isoflurane anesthesia.Abbreviations: BSR, burst suppression ratio; EEG, electroencephalogram; GABA, γ-aminobutyric acid; MAC, minimum alveolar anesthetic concentrationThe electroencephalogram (EEG) shows characteristic temporal patterns under different anesthetic conditions.¹⁷ During deep isoflurane anesthesia, a burst suppression pattern appears in which high-amplitude bursts are followed by periods of nearly silent EEG.^7,11 The burst suppression ratio (BSR) is the percentage of suppression (silent EEG) during the burst suppression pattern and is used to assess anesthesia depth.^11,15 We and others have shown late evoked burst responses synchronized to external stimuli, which might represent unconscious sensory processing.^7,8,17 However a systematic analysis of BSR changes in response to different types of stimuli has not been performed. Because external stimulation during isoflurane anesthesia can initiate cortical burst activity, we investigated whether modality and context-specific cortical activation could occur during this state.The mechanisms that underlie BSR pattern generation during isoflurane anesthesia are still under investigation. However several key findings have contributed greatly to our understanding. Cortical neural networks show patterns of spontaneous intrinsic activity in the absence of sensory inputs,⁹ and single-neuron membrane potentials in slice preparations can transit spontaneously between 2 states, termed the ‘up’ and ‘down’ states.³ Transitions between these states are abolished by antagonists for glutamate and γ-aminobutyric acid (GABA) receptors.¹⁹ The silent periods of the isoflurane-induced burst suppression activity may be due to long periods of hyperpolarization caused either by inhibition of glutamate-mediated excitatory potentials or by increased GABA receptor-mediated inhibition.^12,22 Isoflurane inhibits voltage-gated sodium channel currents and suppresses the release of glutamate through these blocked channels.²² In addition, the mechanisms that drive suppression periods during isoflurane anesthesia likely involve GABA-gated chloride currents and could also involve increased potassium channel conductance, leading to a reduction of excitatory synaptic input.¹² Evidence also suggests that isoflurane may affect cortical input less than cortical output.⁵Because specific types of memory can be acquired during isoflurane anesthesia, limited sensory processing may be possible during this state.¹⁰ In addition, certain aspects of cortical information processing seem to be less sensitive to anesthetics than others; therefore, sensory responsiveness to some stimuli may be blocked less effectively by anesthetics at lower doses than other types of sensation, such as painful stimuli.¹ Cortical responsiveness during isoflurane anesthesia may result from a decreased threshold of activation through specific thalamic pathways. Despite the observation that unresponsive conditions are characterized by hyperpolarized thalamic nuclei,¹⁶ sensory stimulation during isoflurane anesthesia can still evoke the appearance of synchronized bursts during burst suppression periods.^7,8 In addition, burst activation may parallel an arousal mechanism, which could remain selectively active during isoflurane anesthesia.²¹In this experiment, we recorded the EEG continuously in isoflurane-anesthetized Sprague–Dawley rats while applying different types of external auditory stimulation. We hypothesized that external auditory stimulation can elicit modality-specific cortical activation and that some types of sensory discrimination might occur during this state.     

Automatic Realistic Real Time Stimulation/Recording in Weakly Electric Fish: Long Time Behavior Characterization in Freely Swimming Fish and Stimuli Discrimination

Weakly electric fish are unique model systems in neuroethology, that allow experimentalists to non-invasively, access, central nervous system generated spatio-temporal electric patterns of pulses with roles in at least 2 complex and incompletely understood abilities: electrocommunication and electrolocation. Pulse-type electric fish alter their inter pulse intervals (IPIs) according to different behavioral contexts as aggression, hiding and mating. Nevertheless, only a few behavioral studies comparing the influence of different stimuli IPIs in the fish electric response have been conducted. We developed an apparatus that allows real time automatic realistic stimulation and simultaneous recording of electric pulses in freely moving Gymnotus carapo for several days. We detected and recorded pulse timestamps independently of the fish’s position for days. A stimulus fish was mimicked by a dipole electrode that reproduced the voltage time series of real conspecific according to previously recorded timestamp sequences. We characterized fish behavior and the eletrocommunication in 2 conditions: stimulated by IPIs pre-recorded from other fish and random IPI ones. All stimuli pulses had the exact Gymontus carapo waveform. All fish presented a surprisingly long transient exploratory behavior (more than 8 h) when exposed to a new environment in the absence of electrical stimuli. Further, we also show that fish are able to discriminate between real and random stimuli distributions by changing several characteristics of their IPI distribution.     

Modeling the Emergence of Whisker Direction Maps in Rat Barrel Cortex

Based on measuring responses to rat whiskers as they are mechanically stimulated, one recent study suggests that barrel-related areas in layer 2/3 rat primary somatosensory cortex (S1) contain a pinwheel map of whisker motion directions. Because this map is reminiscent of topographic organization for visual direction in primary visual cortex (V1) of higher mammals, we asked whether the S1 pinwheels could be explained by an input-driven developmental process as is often suggested for V1. We developed a computational model to capture how whisker stimuli are conveyed to supragranular S1, and simulate lateral cortical interactions using an established self-organizing algorithm. Inputs to the model each represent the deflection of a subset of 25 whiskers as they are contacted by a moving stimulus object. The subset of deflected whiskers corresponds with the shape of the stimulus, and the deflection direction corresponds with the movement direction of the stimulus. If these two features of the inputs are correlated during the training of the model, a somatotopically aligned map of direction emerges for each whisker in S1. Predictions of the model that are immediately testable include (1) that somatotopic pinwheel maps of whisker direction exist in adult layer 2/3 barrel cortex for every large whisker on the rat''s face, even peripheral whiskers; and (2) in the adult, neurons with similar directional tuning are interconnected by a network of horizontal connections, spanning distances of many whisker representations. We also propose specific experiments for testing the predictions of the model by manipulating patterns of whisker inputs experienced during early development. The results suggest that similar intracortical mechanisms guide the development of primate V1 and rat S1.     

Improved Discrimination of Visual Stimuli Following Repetitive Transcranial Magnetic Stimulation

Background

Repetitive transcranial magnetic stimulation (rTMS) at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a “virtual lesion” in stimulated brain regions, with correspondingly diminished behavioral performance.

Methodology/Principal Findings

Here we investigated the effects of rTMS to visual cortex on subjects'' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz) stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task.

Conclusions/Significance

Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception.     

Coherence between Rat Sensorimotor System and Hippocampus Is Enhanced during Tactile Discrimination

Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5–12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats—whisker motion, hippocampal local field potential (LFP), and barrel cortex unit firing—during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task). Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers.     

胡须信息在大鼠双侧初级体感皮层间的传递路径

大鼠的初级体感皮层(primary somatosensory cortex,SⅠ)虽然只接受来自对侧胡须的上行输入,但仍可以被同侧胡须刺激所激活.解剖学研究发现,在两侧SⅠ皮层之间有两条传递胡须信息胼胝体通路:一条是类颗粒区(perigranular zone,PGZ)通路;另一条是异颗粒区(dysgranular zone,DZ)通路.然而,哪一条通路在传递胡须刺激信息的过程中起主要作用还不清楚.本研究使用电压敏感染料(voltage-sensitive dye,VSD)成像技术来观察胡须刺激时整个SⅠ的神经元群体活动的空间分布和时间特性.实验发现,对侧胡须刺激首先激活barrel(颗粒区,granular zone,GZ),然后以兴奋波的形式传播到胡须感觉区(sub-barrel field cortex,BFC)外侧的DZ.而与首先激活BFC的对侧胡须刺激不同,同侧胡须刺激首先激活SⅠ的DZ.所激发的皮层兴奋以波的形式传播并扩散至BFC.失活另一侧皮层可以抑制这种同侧反应.电刺激另一侧半球皮层与刺激同侧胡须类似,也首先激活成像侧DZ.我们的实验结果显示,胡须刺激激活对侧SⅠ,在经过胼胝体传导后,另一侧半球的DZ(同侧于被刺激的胡须)被激活.连接双侧皮层DZ区的胼胝体连接在SⅠ对同侧胡须刺激的反应中起了主导作用.     

Whisker Movements Reveal Spatial Attention: A Unified Computational Model of Active Sensing Control in the Rat

Spatial attention is most often investigated in the visual modality through measurement of eye movements, with primates, including humans, a widely-studied model. Its study in laboratory rodents, such as mice and rats, requires different techniques, owing to the lack of a visual fovea and the particular ethological relevance of orienting movements of the snout and the whiskers in these animals. In recent years, several reliable relationships have been observed between environmental and behavioural variables and movements of the whiskers, but the function of these responses, as well as how they integrate, remains unclear. Here, we propose a unifying abstract model of whisker movement control that has as its key variable the region of space that is the animal''s current focus of attention, and demonstrate, using computer-simulated behavioral experiments, that the model is consistent with a broad range of experimental observations. A core hypothesis is that the rat explicitly decodes the location in space of whisker contacts and that this representation is used to regulate whisker drive signals. This proposition stands in contrast to earlier proposals that the modulation of whisker movement during exploration is mediated primarily by reflex loops. We go on to argue that the superior colliculus is a candidate neural substrate for the siting of a head-centred map guiding whisker movement, in analogy to current models of visual attention. The proposed model has the potential to offer a more complete understanding of whisker control as well as to highlight the potential of the rodent and its whiskers as a tool for the study of mammalian attention.     

Coyote Investigative Behavior Following Removal of Novel Stimuli

ABSTRACT Because coyotes (Canis latrans) show an aversion to novel objects, we examined the effects of the presence and removal of repellent and attractive stimuli on coyote behavior. We found a greater proportion of captive coyotes investigated 10-cm-tall cones (0.95) compared to 90-cm-tall cones (0.68) and control sites (0.81), and spent longer periods (P < 0.001 in all instances) investigating small cones (x̄ = 465 sec), compared to large cones (x̄ = 212 sec) and control sites (x̄ = 45 sec). However, investigation times at sites following removal of large cones were 1.6 and 2.3 times greater than investigation times at sites following removal of small cones and the control, respectively. Results from pen studies were supported by a field study. Wild coyotes in south Texas visited 43% of small cones but did not visit large cones. Following removal of cones, visits to small cone stations decreased to 29%, whereas coyotes visited 43% of large cone stations. Thus, we observed a direct relationship between aversion toward large novel objects and subsequent attraction to sites following their removal among both captive and wild coyotes. Based upon our results, we suggest that placing large novel objects over traps that are set and removing such objects after a few days, with the subsequent addition of an olfactory attractant, may increase exploratory behavior and capture of coyotes.     

Self-selection of Dietary Threonine in the Rat and the Effect of Taste Stimuli on its Selection

The possible regulation of dietary threonine intake and the effect of a palatable (sodium saccharin) or aversive (quinine sulfate) taste stimulus on the manner of threonine selection were investigated in rats using a self-selection feeding method. Weanling rats were offered the choice of two diets differing only in threonine content for 2 weeks. Both weight gain and food consumption in the rats offered the choice of diets were quite comparable to each other and were the same as those in rats fed one diet containing sufficient threonine. Threonine intake of the self-selecting rats ranged from 0.43 to 1.90% of the food consumed. The threonine concentrations in the plasma and brain of the self-selecting rats increased proportionally with the threonine intake. When rats were offered a choice of two diets containing various amounts of threonine with taste materials, i.e., sodium saccharin or quinine sulfate, neither the dietary threonine nor their growth were ever affected.

These results indicate clearly that rats have an ability to regulate threonine intake to meet their requirement for the l-amino acid, and the threonine selection is not influenced significantly by the dietary addition of palatable or aversive taste materials.     

Effect of Inflammatory Stimuli on the Silver Staining Pattern of the Rat Carotid Endothelium

Silver nitrate stains the intercellular junctions of the endothelium and other cytoplasmic or membrane components. Two protocols are described for the silver staining of rat carotid endothelium that exclude the use of pressurized fixatives and simplify the technique previously described for rat aorta. The entire surface of the carotid endothelium was examined and several parameters (stigmata, granularity, clustering of anionic sites, transversal lines, weakening of silver lines and leukocyte adhesion) were evaluated. We studied the pattern of silver staining in two situations: (1) endothelial activation and (2) neurogenic inflammation. Endothelial activation was produced by the intravenous administration of a proinflammatory albumin or polyinosinic acid. Both products cause a marked increase in leukocyte adhesion concomitant with a decrease in argyrophilia and a weakness or loss of silver lines. Neurogenic inflammation, which is mediated by substances released from sensory nerves, was induced by the intravenous administration of substance P or capsaicin. Both stimuli produced an increase in argyrophilia and weakness or loss of silver lines. Substance P caused a clustering of anionic sites, whereas this phenomenon was more discrete with capsaicin. Nearly 80% of all examined rats (controls and inflammatory stimuli treated) showed endothelial membrane disruptions formed by clusters of cells often in the shape of streaks aligned with the long axis of the vessel. The detection of these discontinuities is important, as loss of endothelial integrity is central in the initiation of pathological events.     

Circadian Discrimination of Reward: Evidence for Simultaneous Yet Separable Food- and Drug-Entrained Rhythms in the Rat

A unique extra-suprachiasmatic nucleus (SCN) oscillator, operating independently of the light-entrainable oscillator, has been hypothesized to generate feeding and drug-related rhythms. To test the validity of this hypothesis, sham-lesioned (Sham) and SCN-lesioned (SCNx) rats were housed in constant dim-red illumination (LL_red) and received a daily cocaine injection every 24?h for 7 d (Experiment 1). In a second experiment, rats underwent 3-h daily restricted feeding (RF) followed 12 d later by the addition of daily cocaine injections given every 25?h in combination with RF until the two schedules were in antiphase. In both experiments, body temperature and total activity were monitored continuously. Results from Experiment 1 revealed that cocaine, but not saline, injections produced anticipatory increases in temperature and activity in SCNx and Sham rats. Following withdrawal from cocaine, free-running temperature rhythms persisted for 2–10 d in SCNx rats. In Experiment 2, robust anticipatory increases in temperature and activity were associated with RF and cocaine injections; however, the feeding periodicity (23.9?h) predominated over the cocaine periodicity. During drug withdrawal, the authors observed two free-running rhythms of temperature and activity that persisted for >14 d in both Sham and SCNx rats. The periods of the free-running rhythms were similar to the feeding entrainment (period?=?23.7 and 24.0?h, respectively) and drug entrainment (period?=?25.7 and 26.1?h, respectively). Also during withdrawal, the normally close correlation between activity and temperature was greatly disrupted in Sham and SCNx rats. Taken together, these results do not support the existence of a single oscillator mediating the rewarding properties of both food and cocaine. Rather, they suggest that these two highly rewarding behaviors can be temporally isolated, especially during drug withdrawal. Under stable dual-entrainment conditions, food reward appears to exhibit a slightly greater circadian influence than drug reward. The ability to generate free-running temperature rhythms of different frequencies following combined food and drug exposures could reflect a state of internal desynchrony that may contribute to the addiction process and drug relapse. (Author correspondence: heiko@vetmed.wsu.edu)     

Ultrasonic Vocalizations in Rat Sexual Behavior

Ultrasonic vocalizations are very conspicuous during rat matingactivity. Two types of calls are produced by both sexes. Thefirst, brief complex calls with the main frequency centeredabout 50 kHz, occur primarily in conjunction with solicitationand mounting activity. The second type of call is the long,22 kHz whistle which is emitted mainly by the male during thepostejaculatory refractory period, but also by both male andfemale at other times during the copulatory sequence. The occurrenceof ultrasonic vocalizations is correlated with sexual motivationof rats. Males emit more 50 kHz calls before successful matingtests than before tests in which they fail to ejaculate. Furthermore,more vocalizations are emitted by the pair prior to intromissionsthan prior to mounts without intromission. Just before ejaculationthere is a large increase in the rate of calling and, at times,transition by the male to calling at 22 kHz. This latter eventmay represent physiological dearousal by the male. Followingejaculation, the male characteristically emits 22 kHz vocalizationsand exhibits a sleep-like EEG pattern. The function of the postejaculatoryvocalization may be to enforce separation between the matingpair, while at the same lime maintaining contact between thepartners. Fifty kHz calls, on the other hand, prime and facilitatesexual responsiveness of the female. Tape recorded vocalizationsof mating rats facilitate solicitation behavior of estrous femalesin the presence of castrated males, and such females also showa preference for these sounds in a "Y" maze. Deafening of femalesdoes not affect their normal pacing of copulatory contacts,but it drastically reduces their solicitation behavior. Thestudies summarized in this paper lead us to conclude that ultrasonicvocalizations play a major role in the integration of reproductiveactivity in the Norway rat, Rattus norvegicus.     

Similar Odor Discrimination Behavior in Head-Restrained and Freely Moving Mice

A major challenge in neuroscience is relating neuronal activity to animal behavior. In olfaction limited techniques are available for these correlation studies in freely moving animals. To solve this problem, we developed an olfactory behavioral assay in head-restrained mice where we can monitor behavioral responses with high temporal precision. Mice were trained on a go/no-go operant conditioning paradigm to discriminate simple monomolecular odorants, as well as complex odorants such as binary mixtures of monomolecular odorants or natural odorants. Mice learned to discriminate both simple and complex odors in a few hundred trials with high accuracy. We then compared the discrimination performance of head-restrained mice to the performance observed in freely moving mice. Discrimination accuracies were comparable in both behavioral paradigms. In addition, discrimination times were measured while the animals performed well. In both tasks, mice discriminated simple odors in a few hundred milliseconds and took additional time to discriminate the complex mixtures. In conclusion, mice showed similar and efficient discrimination behavior while head-restrained compared with freely moving mice. Therefore, the head-restrained paradigm offers a relevant approach to monitor neuronal activity while animals are actively engaged in olfactory discrimination behaviors.     

Vibrotactile temporal summation: effect of frequency.

Temporal summation of vibrotactile stimuli was measured at four frequencies (25, 40, 80, and 160 Hz) using a large contactor. Stimulation at 160 Hz gave temporal summation comparable in amount to that reported in previous studies. Stimulation at 25, 40, and 80 Hz gave less summation. The presence of summation at low frequencies is unexpected in view of existing data obtained with small contactors' those data indicate that the afferent system primarily sensitive to low frequencies may not summate stimulus energy over time. The present data suggest either that the low-frequency afferents do summate energy over time or that, under some conditions, the perception of low-frequency signals presented through a large contactor may be mediated by more than one afferent system.     

Irrelevant Stimuli and Action Control: Analyzing the Influence of Ignored Stimuli via the Distractor-Response Binding Paradigm

Selection tasks in which simple stimuli (e.g. letters) are presented and a target stimulus has to be selected against one or more distractor stimuli are frequently used in the research on human action control. One important question in these settings is how distractor stimuli, competing with the target stimulus for a response, influence actions. The distractor-response binding paradigm can be used to investigate this influence. It is particular useful to separately analyze response retrieval and distractor inhibition effects. Computer-based experiments are used to collect the data (reaction times and error rates). In a number of sequentially presented pairs of stimulus arrays (prime-probe design), participants respond to targets while ignoring distractor stimuli. Importantly, the factors response relation in the arrays of each pair (repetition vs. change) and distractor relation (repetition vs. change) are varied orthogonally. The repetition of the same distractor then has a different effect depending on response relation (repetition vs. change) between arrays. This result pattern can be explained by response retrieval due to distractor repetition. In addition, distractor inhibition effects are indicated by a general advantage due to distractor repetition. The described paradigm has proven useful to determine relevant parameters for response retrieval effects on human action.     

Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex

Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1) during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation.