Corneal Airpuff Unconditioned Stimulus Research Articles

Transfer of classical eyeblink conditioning with electrical stimulation of mPFC or tone as conditioned stimulus in guinea pigs

Learning with a stimulus from one sensory modality can facilitate subsequent learning with a new stimulus from a different sensory modality. To date, the characteristics and mechanism of this phenomenon named transfer effect still remain ambiguous. Our previous work showed that electrical stimulation of medial prefrontal cortex (mPFC) as a conditioned stimulus (CS) could successfully establish classical eyeblink conditioning (EBC). The present study aimed to (1) observe whether transfer of EBC learning would occur when CSs shift between central (mPFC electrical stimulation as a CS, mPFC-CS) and peripheral (tone as a CS, tone CS); (2) compare the difference in transfer effect between the two paradigms, delay EBC (DEBC) and trace EBC (TEBC). A total of 8 groups of guinea pigs were tested in the study, including 4 experimental groups and 4 control groups. Firstly, the experimental groups accepted central (or peripheral) CS paired with corneal airpuff unconditioned stimulus (US); then, CS shifted to the peripheral (or central) and paired with US. The control groups accepted corresponding central (or peripheral) CS and pseudo-paired with US, and then shifted CS from central (or peripheral) to peripheral (or central) and paired with US. The results showed that the acquisition rates of EBC were higher in experimental groups than in control groups after CS switching from central to peripheral or vice versa, and the CR acquisition rate was remarkably higher in DEBC than in TEBC in both transfer ways. The results indicate that EBC transfer can occur between learning established with mPFC-CS and tone CS. Memory of CS–US association for delay paradigm was less disturbed by the sudden switch of CS than for trace paradigm. This study provides new insight into neural mechanisms underlying conditioned reflex as well as the role of mPFC.

Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs

To determine whether electrical stimulation of caudal medial prefrontal cortex (mPFC) as conditioned stimulus (CS) paired with airpuff unconditioned stimulus (US) was sufficient for establishing eyeblink conditioning in guinea pigs, and whether it was dependent on cerebellar interpositus nucleus. Thirty adult guinea pigs were divided into 3 conditioned groups, and trained on the delay eyeblink conditioning, short-trace eyeblink conditioning, and long-trace eyeblink conditioning paradigms, respectively, in which electrical stimulation of the right caudal mPFC was used as CS and paired with corneal airpuff US. A pseudo conditioned group of another 10 adult guinea pigs was given unpaired caudal mPFC electrical stimulation and the US. Muscimol (1 μg in 1 μL saline) and saline (1 μL) were infused into the cerebellar interpositus nucleus of the animals through the infusion cannula on d 11 and 12, respectively. The 3 eyeblink conditioning paradigms have been successfully established in guinea pigs. The animals acquired the delay and short-trace conditioned responses more rapidly than long-trace conditioned responses. Muscimol infusion into the cerebellar interpositus nucleus markedly impaired the expression of the 3 eyeblink conditioned responses. Electrical stimulation of caudal mPFC is effective CS for establishing eyeblink conditioning in guinea pigs, and it is dependent on the cerebellar interpositus nucleus.

Evaluation of bidirectional interstimulus interval (ISI) shift in auditory delay eye-blink conditioning in healthy humans

Delay eye-blink conditioning is an associative learning task that can be utilized to probe the functional integrity of the cerebellum and related neural circuits. Typically, a single interstimulus interval (ISI) is utilized, and the amplitude of the conditioned response (CR) is the primary dependent variable. To study the timing of the CR, an ISI shift can be introduced (e.g., shifting the ISI from 350 to 850ms). In each phase, a conditioned stimulus (e.g., a 400- or 900-ms tone) coterminates with a 50-ms corneal air puff unconditioned stimulus. The ability of a subject to adjust the CR to the changing ISI constitutes a critical timing shift. The feasibility of this procedure was examined in healthy human participants (N = 58) using a bidirectional ISI shift procedure while cortical event-related brain potentials were measured. CR acquisition was faster and the responses better timed when a short ISI was used. After the ISI shift, additional training was necessary to allow asymptotic responding at the new ISI. Interestingly, auditory event-related potentials to the CR were not associated with conditioning measures at either ISI.

Analysis of long-term cognitive-enhancing effects of bryostatin-1 on the rabbit (Oryctolagus cuniculus) nictitating membrane response

Previous work demonstrated that protein kinase C (PKC) is implicated in learning and memory. This study investigated whether: (i) PKC activated by bryostatin-1 (Bryo) just before or just after sessions of classical conditioning was capable of enhancing classical conditioning of the rabbit nictitating membrane response; (ii) improved behavioral performance matched the time course of PKC activation induced by Bryo; and (iii) vitamin E (Vit E) enhanced the efficacy of Bryo. Paired rabbits received daily trace conditioning with a tone conditioned stimulus and a corneal air puff unconditioned stimulus. Unpaired rabbits received the same stimuli but in an explicitly unpaired manner. After trace conditioning, all rabbits received daily delay conditioning, and then tone intensity testing. Rabbits pretreated with 10 microg/kg Bryo every other day before a relatively simple trace conditioning task showed more conditioned responses (CRs) during the first 10 trials of each trace conditioning session and a higher likelihood of a CR on the first trial of each trace conditioning session than rabbits pretreated with the vehicle control. Rabbits either posttreated daily with 10 microg/kg Bryo or pretreated with Vit E and subjected to a difficult trace conditioning task showed increased CRs relative to the vehicle control. Neither Bryo nor Vit E or their combination altered nonassociative responding or altered sensitivity to the conditioned stimulus or unconditioned stimulus. These findings demonstrate Bryo has long-term enhancing effects on classical conditioning of the rabbit nictitating membrane response.

Cannabis Use Disrupts Eyeblink Conditioning: Evidence for Cannabinoid Modulation of Cerebellar-Dependent Learning

While the cerebellum contains the highest density of cannabinoid receptor (CB1) in the brain, no studies have assessed the effect of exogenous cannabinoids on cerebellar-dependent learning in humans. The current study, therefore, examined the effect of chronic cannabis use on classical eyeblink conditioning (EBC), a cerebellar-mediated task which has been shown to be disrupted in CB1 knockout mice. Chronic cannabis users (24 h abstinence before study; positive THC urine drug test) free of DSM-IV Axis-I or -II disorders, were evaluated. A delay EBC task was utilized, in which a conditioned stimulus (CS; 400 ms tone) co-terminated with a corneal air puff unconditioned stimulus (US; 50 ms), thus eliciting a conditioned blink response (CR). The cannabis group exhibited markedly fewer, and more poorly timed CRs as compared to drug-naive controls. There were no differences between the groups in either the unconditioned response (UR) or an EEG measure of selective attention to the CS (N100 auditory ERP), indicating that the disruption observed in the cannabis group was specific to CR acquisition. These results suggest that cannabis use is associated with functional deficits in the cerebellar circuitry underlying EBC, a finding which corroborates the recent work in CB1 knockout mice.

Aging and learning-specific changes in single-neuron activity in CA1 hippocampus during rabbit trace eyeblink conditioning.

Rabbit trace eyeblink conditioning is a hippocampus-dependent task in which the auditory conditioned stimulus (CS) is separated from the corneal airpuff unconditioned stimulus (US) by a 500-ms empty trace interval. Young rabbits are able to associate the CS and US and acquire trace eyeblink conditioned responses (CRs); however, a subset of aged rabbits show poor learning on this task. Several studies have shown that CA1-hippocampal activity is altered by aging; however, it is unknown how aging affects the interaction of CA1 single neurons within local ensembles during learning. The present study examined the extracellular activity of CA1 pyramidal neurons within local ensembles in aged (29-34 mo) and young (3-6 mo) rabbits during 10 daily sessions (80 trials/session) of trace eyeblink conditioning. A single surgically implanted nonmovable stereotrode was used to record ensembles ranging in size from 2 to 12 separated single neurons. A total of six young and four aged rabbits acquired significant levels of CRs, whereas five aged rabbits showed very few CRs similar to a group of five young pseudoconditioned rabbits. Pyramidal cells (2,159 total) were recorded from these four groups during training. Increases in CA1 pyramidal cell firing to the CS and US were diminished in the aged nonlearners. Local ensembles from all groups contained heterogeneous types of pyramidal cell responses. Some cells showed increases while others showed decreases in firing during the trace eyeblink trial. Hierarchical clustering was used to isolate seven different classes of single-neuron responses that showed unique firing patterns during the trace conditioning trial. The proportion of cells in each group was similar for six of seven response classes. Unlike the excitatory modeling patterns reported in previous studies, three of seven response types (67% of recorded cells) exhibited some type of inhibitory decrease to the CS, US, or both. The single-neuron response classes showed different patterns of learning-related activity across training. Several of the single-neuron types from the aged nonlearners showed unique alterations in response magnitude to the CS and US. Cross-correlation analyses suggest that specific single-neuron types provide more correlated single-neuron activity to the ensemble processing of information. However, aged nonlearners showed a significantly lower level of coincident pyramidal cell firing for all cell types within local ensembles in CA1.

Hippocampal lesions prevent trace eyeblink conditioning in the freely moving rat

The effect of hippocampal aspiration lesions on trace eyeblink conditioning was examined in young, freely-moving F1 hybrid rats (Fisher 344×Brown Norway). Rats which received either bilateral neocortical or bilateral hippocampal aspiration lesions were compared with each other or with sham lesioned control rats. The rats were trained with a 250 ms tone conditioning stimulus (CS), a 250 ms stimulus free trace interval and a 100 ms corneal airpuff unconditioned stimulus (US). Rats with lesions of the hippocampus were significantly impaired relative to the neocortical and sham lesioned control rats. Analyses of different behavioral parameters (e.g. percent conditioned responses, amplitude, and area of response) indicated that all of the measures for the conditioned response were significantly impaired by the hippocampal lesion. The unconditioned response was not significantly affected by the lesion, and there was no significant difference among the groups after 2 days of subsequent conditioning with the delay paradigm (zero trace interval). We conclude that the hippocampus is required for rats to learn the association between a tone CS and an airpuff US when a 250 ms trace interval is interposed between the two stimuli.

Hippocampal encoding of non-spatial trace conditioning.

Trace eyeblink classical conditioning is a non-spatial learning paradigm that requires an intact hippocampus. This task is hippocampus-dependent because the auditory tone conditioned stimulus (CS) is temporally separated from the corneal airpuff unconditioned stimulus (US) by a 500-ms trace interval. Our laboratory has performed a series of neurophysiological experiments that have examined the activity of pyramidal cells in the CA1 area of the hippocampus during trace eyeblink conditioning. We have found that the non-spatial stimuli involved in this paradigm are encoded in the hippocampus in a logical order that is necessary for their association and the subsequent expression of behavioral learning. Although there were many profiles of single neurons responding to the CS-US trial during training, the majority of the neurons showed an increase in activity to the airpuff-US. Prior to learning, it appears that hippocampal cells and ensembles of cells were preferentially attending to the stimulus with immediate behavioral importance, the US. Hippocampal cells then began to respond to the associated neutral stimulus, the CS. Shortly thereafter, animals began to show increases in the behavioral expression of CRs. In some experiments, hippocampal neurons from aged animals exhibited impairments in the encoding of CS and US information. These aged animals were not able to associate these stimuli and acquire trace eyeblink CRs. Our findings along with the findings of other spatial learning studies, suggest that the hippocampus is involved in encoding information about discontiguous sets of stimuli, either spatial or nonspatial, especially early in the learning process.

β-Adrenergic involvement in acquisition vs. extinction of a classically conditioned eye blink response in rabbits

β-adrenergic involvement in classical conditioning and extinction was investigated. Five groups of rabbits (saline, 1, 3, 5 or 10 mg kg −1 of the β-adrenergic antagonist propranolol) were trained with a tone conditioned stimulus (CS) paired with a corneal air puff unconditioned stimulus (US). Both 5 mg kg −1 and 10 mg kg −1 propranolol delayed acquisition of conditioned responses but all groups were able to learn the task to criterion. Consistent changes were not seen during extinction.

Sequence of single neuron changes in CA1 hippocampus of rabbits during acquisition of trace eyeblink conditioned responses.

The sequence of changes in single neuron activity in the CA1 area of the rabbit hippocampus was examined during daily sessions (80 trials/session) of hippocampally dependent nonspatial trace eyeblink (i.e., nictitating membrane response) conditioning. Each trial for trace conditioned animals (n = 7) consisted of a tone conditioned stimulus (CS; 6 kHz; 90 dB, 100 ms) followed by a 500-ms silent trace period, then a corneal airpuff unconditioned stimulus (US; 3.0 psi; 150 ms). Control animals (n = 5) received unpaired CSs and USs. Most pyramidal (n = 309) and theta (n = 21) cells were recorded for a single day of training. The activity of cells for each animal were grouped according to: the day of training that CRs began to increase and the day of training that CR performance became asymptotic. Pyramidal cells from trace conditioned animals demonstrated several stages of learning-related activity: large increases in activity after both the CS and US early in conditioning on the day of training when CRs began to increase, smaller moderate increases in activity on the following days of training, and decreases in activity after the US during asymptotic CRs. Pyramidal cell-increases declined significantly across the trials of each daily session. Theta cells showed an activity pattern opposite to the pyramidal cells, consistent with the notion that theta cells have an inhibitory influence on pyramidal cells. Single pyramidal cells also were categorized into response profiles. Most pyramidal response profiles showed increases in activity specific to the day of initial CRs. Two of the pyramidal response profiles may be involved in assessing the temporal properties of the CS-US trace conditioning trial.

Changes of synaptic efficacy in the medial geniculate nucleus as a result of auditory classical conditioning

In this study we examined inputs to neurons in the medial subnucleus of the medial geniculate nucleus (mMG) for changes of synaptic efficacy associated with heart-rate conditioning to an auditory conditioned stimulus (CS). Conditioning-related changes of synaptic efficacy were measured in awake animals by examining mMG single-unit responses evoked by stimulation of one of two areas that send auditory CS and nonauditory information monosynaptically to the mMG, the brachium of the inferior colliculus (BlC) and the superior colliculus (SC). Synaptic efficacy was measured before, immediately after, and 1 hr after one session of classical conditioning with a tone CS and a corneal airpuff unconditioned stimulus. To determine whether conditioning produced changes of synaptic efficacy on the auditory BlC inputs to mMG cells and not general changes of cellular excitability, analyses of synaptic efficacy were performed on the mMG units that exhibited short-latency evoked responses (< 3.5 msec) to both BlC and SC stimulation. Analyses revealed that the BlC but not the SC test stimulus-evoked unit activity from the same neurons exhibited the following changes immediately after conditioning: decreases in unit response latency, increases in unit response reliability, and increases in spike frequency. BlC-evoked unit responses after pseudoconditioning did not exhibit these changes in unit responding. These results suggest that the synapses carrying auditory CS information to mMG neurons increase in strength as the result of associative conditioning with an acoustic CS. Some of these changes of synaptic efficacy remained 1 hr after training.

Immunohistochemical expression of the c-Fos protein in the spinal trigeminal nucleus following presentation of a corneal airpuff stimulus

This study examined the expression of the c-Fos protein in the rabbit's central nervous system to determine which areas are activated by the presentation of a corneal airpuff. Previous work has shown that pairing a corneal airpuff unconditioned stimulus (US) with a tone conditioned stimulus (CS) produces reliable heart rate (HR) conditioning. In this study restrained awake rabbits received 100 corneal airpuffs. Brains were then processed immunohistochemically for the c-Fos protein. In animals that received the airpuff the ventral portion of the ipsilateral spinal trigeminal subnucleus caudalis (SVc) and interpolaris (SVi), and the dorsal raphe nucleus exhibited a greater number of c-Fos labeled cells compared to control animals. Another group of animals was given microinjections of WGA-HRP in the medial nucleus of the medial geniculate (mMG) to determine if this critical auditory area of the HR conditioning circuitry receives projections from SW and SW These injections produced retrograde labeling in the same areas of SW and SVi activated by the airpuff. Thus, a corneal airpuff activates neurons in SVc and SVi which could then activate neurons in mMG. This provides additional evidence that CS and US information converge in mMG.

Destruction of neurons in the VPM thalamus prevents rabbit heart rate conditioning

The present study examined the role of the ventral posterior medial nucleus of the thalamus (VPM) in classical heart rate (HR) conditioning using an acoustic conditioned stimulus (CS) and a corneal air puff unconditioned stimulus (US). Previous research suggests that VPM neurons are activated during the presentation of a corneal air puff US. Rabbits were given ibotenic acid lesions in the VPM and subjected to one Pavlovian HR conditioning session. The results of the present study demonstrate that destruction of cell bodies in the VPM reduces HR conditioning to the level of a pseudoconditioning control without affecting HR baseline, or orienting responses to the CS. Lesions of the VPM also significantly augment the tachycardiac unconditioned response, suggesting that VPM lesions alter the somatosensory processing of the US.

Age-related deficits in retention of the classically conditioned nictitating membrane response in rabbits.

Young and aged rabbits underwent classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS) for 18 consecutive days. Rabbits were then returned to their home cages for a 90-day period in which they received no further conditioning, but they were handled daily. On Day 91 they underwent retention testing during which the CS alone was presented 20 times. This was immediately followed by reacquisition in which the CS and UCS were again paired for 100 trials. Reacquisition was repeated on the following day. As in previous studies, aged rabbits acquired the conditioned response (CR) more slowly than young rabbits; however, by the end of acquisition, both groups reached similar asymptotic levels. Retention of the CR was significantly lower for aged than young rabbits. Reacquisition was also retarded in aged vs. young rabbits. Nonassociative factors, such as sensitivity to the stimuli or general health, could not account for these differences. Data are discussed in terms of using retention of the conditioned eyeblink response as a model system for studying age-related memory deficits.

A substituted pyrrolidinone, BMY 21502, and classical conditioning of the nictitating membrane response in young and older rabbits

New Zealand white rabbits (N = 76; 38 at 3 months, 38 at 21–55 months) were classically conditioned for 10 90-trial sessions in the 750-msec delay paradigm using a tone conditioned stimulus (CS) and corneal airpuff unconditioned stimulus (US). Young and older rabbits were divided into groups receiving paired CS-US presentations with 0, 5, or 10 mg/kg of BMY 21502. Unpaired tone and airpuff presentations were given to control groups administered 0 or 5 mg/kg of BMY 21502. Over training sessions, the older BMY-21502-treated rabbits produced a higher percentage of conditioned responses (CRs) and greater CR amplitude than did the vehicle-treated older rabbits. BMY 21502 did not facilitate conditioning in the young rabbits. There were significant age differences in acquisition between the young and older vehicle-treated animals. Although the BMY-21502-treated older rabbits did not achieve the asymptotic level of performance of the young rabbits, BMY 21502 treatment resulted in conditioning for the older rabbits that was similar to that for the younger rabbits.

A nicotinic agonist (GTS-21), eyeblink classical conditioning and nicotinic receptor binding in rabbit brain

The septo-hippocampal cholinergic system is of demonstrated involvement in eyeblink classical conditioning (EBCC). To determine if a nicotinic cholinergic agonist, GTS-21, would facilitate acquisition of EBCC in older rabbits, three doses (0.1, 0.5, 1.0 mg/kg) in sterile saline vehicle and vehicle alone were administered toolder rabbits ( n = 48; mean age= 29.8 months). A control group of vehicle-treated young rabbits ( n = 12; mean age= 3.5 months) was included. Rabbits were conditioned for fifteen 90-trial sessions in the 750 ms delay paradigm with a tone conditioned stimulus and corneal airpuff unconditioned stimulus. Dependent measures of trials to learning criterion, percentage of conditioned responses (CRs) and CR amplitude consistently showed significant improvement in older rabbits treated with 0.5 and 1.0 mg/kg of GTS-21. Acquisition was similar in vehicle-treated young and GTS-treated older rabbits. Vehicle-treated older rabbits conditioned more poorly than vehicle-treated young rabbits. No non-associative learning effects were observed in GTS-21 treated animals. Nicotinic receptor binding was similar in all groups of older rabbits, indicating that GTS-21 administration over a 15-day period did not affect nicotinic receptors. Alzheimer's disease (AD) has been associated with significant loss of nicotinic cholinergic receptors, and patients diagnosed with probable AD are seriously impaired on EBCC. These results demonstrating that the nicotinic agonist, GTS-21, facilitated EBCC in older rabbits suggest that the compound should receive additional investigation for its potential to affect cognition in AD.

Nefiracetam (DM-9384): effect on eyeblink classical conditioning in older rabbits.

The nootropic compound nefiracetam was evaluated in 88 older rabbits in a 750-ms delay paradigm of eyeblink classical conditioning (EBCC). Rabbits (mean age = 28.7 months) were assigned in groups of eight to one of six conditions in experiment 1: paired tone conditioned stimulus (CS)-corneal airpuff unconditioned stimulus (US) presentations and 1, 3, or 10 mg nefiracetam/kg or sterile saline vehicle; explicitly unpaired CS and US presentations and 3 mg nefiracetam/kg or sterile saline vehicle. Animals in the paired conditions received 10 daily sessions of 90 paired trials and animals in the unpaired conditions received 10 daily sessions of 180 unpaired CS and US presentations. The six conditions in experiment 2 were 5, 10, and 15 mg nefiracetam/kg and vehicle in 15 sessions of paired presentations; 10 mg nefiracetam/kg and vehicle in 15 sessions of unpaired conditioning. In both experiments 1 and 2, acquisition measured by trials to learning criterion was significantly faster at the 10 mg/kg dose of nefiracetam. In the repeated measures analyses comparing six doses in the paired conditions, all dependent measures [percentage conditioned responses (CRs), CR amplitude, and response latency] indicated significantly better conditioning in rabbits treated with 10 mg nefiracetam/kg, but this dose did not increase motor responding or responding in the unpaired condition. Nefiracetam facilitated acquisition of EBCC in older rabbits. EBCC is performed poorly by older humans and is seriously impaired in Alzheimer's disease. These preclinical data in an animal model with clear parallels in humans suggest that nefiracetam may prove effective as a cognition enhancer in clinical trials.

Harmaline-induced impairment of Pavlovian conditioning in the rabbit

In this study we examined the effects of harmaline on Pavlovian conditioning of the rabbit's nictitating membrane response. The acquisition of conditioned responses was determined during a single session consisting of 120 pairings of a tone-conditioned stimulus with a corneal air puff unconditioned stimulus. Harmaline severely retarded (5 mg/kg) or completely blocked (10 and 20 mg/kg) acquisition of conditioned responses. The blocked or retarded acquisition of conditioned responses could still be detected when the rabbits were tested 2 d after cessation of drug injections, suggesting that harmaline was affecting acquisition and not the motoric expression of conditioned responses. Control experiments established that harmaline (5 mg/kg) did not affect (1) baseline levels of responding, (2) the level of non-associative responding to the conditioned stimulus, (3) the amplitude or any of the temporal characteristics of the unconditioned response, (4) the development of habituation to the unconditioned stimulus, and (5) the threshold of the unconditioned stimulus for eliciting the unconditioned response. However, harmaline did produce a 12 dB increase in the intensity threshold of the conditioned stimulus for eliciting conditioned responses. We concluded that the primary effect of harmaline was to impair stimulus processing within brainstem circuits such as to reduce the excitatory properties of the conditioned stimulus, thus retarding its entry into associative learning. The results were discussed with respect to the possible role of the inferior olive in associative learning.

Disruption of human eyeblink conditioning after central cholinergic blockade with scopolamine.

Human (Homo sapiens) volunteers (N = 72) received saline, a low dose of oral scopolamine (0.6 mg), a high dose of oral scopolamine (1.2 mg), or a peripheral analogue (glycopyrrolate). They then underwent classical conditioning of the eyeblink response to a tone conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS) in a delay conditioning paradigm. There was a dose-related decline in acquisition of the conditioned response. These drug-induced conditioning deficits were similar to those previously reported in rabbit eyeblink conditioning and could not be attributed to such nonassociative factors as changes in auditory thresholds to the tone CS, magnitude of reflexive blinks to the airpuff UCS, or to changes in spontaneous blink rates.

Cochlear nucleus, inferior colliculus, and medial geniculate responses during the behavioral detection of threshold-level auditory stimuli in the rabbit.

Rabbits were conditioned to respond behaviorally to auditory stimuli by pairing a white-noise conditioned stimulus (CS) with a corneal airpuff unconditioned stimulus (US). The conditioned response (CR) was movement of the nictitating membrane (NM). After the subjects were responding at better than the 90% correct level, the intensity of the auditory stimulus was reduced to behavioral threshold using a staircase procedure. Simultaneous measurements of neural unit activity and behavioral NM responses were then made in rabbits performing at behavioral threshold. After the experiment was completed neural unit responses during behavioral detection trials were compared to neural responses made during nondetection trials. Neural unit responses to a constant intensity, white-noise stimulus at behavioral threshold were well defined and essentially identical on behavioral detection and nondetection trials in the ventral cochlear nucleus, the ventrolateral division of the central nucleus of the inferior colliculus, and the ventral division of the medial geniculate body. This suggests that an auditory stimulus can be neuronally "detected" without being behaviorally detected, and that the neural "decision" to respond behaviorally is not made in these nuclei. Responses recorded from the dorsomedial division of the central nucleus of the inferior colliculus, the pericentral nucleus of the inferior colliculus, and less commonly in the medial division of the medial geniculate body were also clearly present and nearly identical during the onset of the auditory stimulus, but were sometimes consistently different for detection and nondetection conditions during the latter part of the auditory stimulus. These brain regions appear to receive both auditory and nonauditory inputs, and show responses which are more highly correlated with detection behavior.