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T H Brown

Publications and source records attributed to T H Brown.

At least 19 recordsLinked to original sources
PubMed2007

Immunohistochemical study of nuclear factor-kappaB activity and interleukin-8 abundance in oesophageal adenocarcinoma; a useful strategy for monitoring these biomarkers.

AIMS: To determine if immunohistochemistry (IHC) could be used to monitor nuclear factor-kappaB (NF-kappaB) activity in oesophageal adenocarcinoma and pre-malignant (Barrett's) oesophageal tissues, relative to normal oesophageal mucosa. The pro-inflammatory cytokine interleukin-8 (IL-8), a transcriptional target of NF-kappaB, was also studied to better understand NF-kappaB functionality; its RNA and protein levels were assessed in oesophageal tissues. METHODS: IHC was employed using an antibody against the nuclear localisation sequence (NLS) of the p65 subunit as well as an antibody against IL-8. To assess NF-kappaB function, changes in gene expression of NF-kappaB controlled genes (IL-8 and I-kappaB) were also assessed in the histological sequence using real-time PCR. More global expression changes were also studied using membrane arrays. RESULTS: IHC was effective at monitoring overall NF-kappaB activity and IL-8 abundance. This method also allowed NF-kappaB activity and IL-8 abundance to be pinpointed in specific cell types. There were significant increases in nuclear NF-kappaB activity and IL-8 abundance across the histological series. Gene expression analysis also showed consistent up-regulation of IL-8, confirming the IHC data and showing enhanced transcriptional NF-kappaB activity. I-kappaB (another NF-kappaB target) showed down-regulation in dysplastic and adenocarcinoma tissues. Down-regulation of I-kappaB gene expression may partly explain increased NF-kappaB activity. CONCLUSION: IHC, using antibodies against the NLS of p65, may be useful in monitoring overall NF-kappaB activity in oesophageal tissues. As IHC is amenable to high-throughput screening (whereas traditional electrophoretic mobility shift assay methods are not), this may lead to the development of a better screening tool for early cancer risk.

Adenocarcinoma↗
PubMed2005

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori.

In this series of experiments, a novel protocol was developed whereby gastric cells were collected using endoscopic cytology brush techniques, and prepared, such that interphase fluorescence in situ hybridization (FISH) could be performed. In total, 80 distinct histological samples from 37 patients were studied using four chromosome probes (over 32,000 cells analysed). Studies have previously identified abnormalities of these four chromosomes in upper GI tumours. Using premalignant tissues, we aimed to determine how early in Correa's pathway to gastric cancer these chromosome abnormalities occurred. Aneuploidy of chromosomes 4, 8, 20 and 17(p53) was detected in histologically normal gastric mucosa, as well as in gastritis, intestinal metaplasia, dysplasia and cancer samples. The levels of aneuploidy increased as disease severity increased. Amplification of chromosome 4 and chromosome 20, and deletion of chromosome 17(p53) were the more common findings. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. Helicobacter pylori infection was determined in premalignant tissue using histological analysis and PCR technology. Detection rates were comparable. PCR was used to subtype H. pylori for CagA status. The amplification of chromosome 4 in gastric tissue was significantly more prevalent in H. pylori-positive patients (n=7) compared to H. pylori-negative patients (n=11), possibly reflecting a role for chromosome 4 amplification in H. pylori-induced gastric cancer. The more virulent CagA strain of H. pylori was associated with increased disease pathology and chromosomal abnormalities, although numbers were small (CagA+ n=3, CagA- n=4). Finally, in vitro work demonstrated that the aneuploidy induced in a human cell line after exposure to the reactive oxygen species (ROS) hydrogen peroxide was similar to that already shown in the gastric cancer pathway, and may further strengthen the hypothesis that H. pylori causes gastric cancer progression via an ROS-mediated mechanism.

Aged↗
PubMed2004

Endoscopic placement of fibrin sealant as a treatment for a long-standing Boerhaave's fistula.

A 64-year-old man suffered a spontaneous rupture of the esophagus (Boerhaave's syndrome) after an episode of severe retching. He underwent attempted primary repair of the esophageal defect, but unfortunately the repair failed with the development of a persistent esophago-bronchial fistula resistant to extended conservative management. Three hundred and nineteen days after the initial rupture, the fistula was successfully treated with endoscopic placement of fibrin glue. We believe this to be the first reported case of fibrin sealant being used in the treatment of a long-standing fistula resulting from Boerhaave's syndrome.

Bronchial Fistula↗
PubMed2001

Predominance of late-spiking neurons in layer VI of rat perirhinal cortex.

Recent work demonstrated the importance of perirhinal cortex (PR) in a variety of behavioral tasks and disease processes. Studies from our laboratory revealed that some layers of PR contain neurons with unusual properties. Here we report a detailed examination of the cellular neurobiology of layer VI of PR, using whole-cell recordings and biocytin cell fills in horizontal rat brain slices. The most striking finding is that an overwhelming majority ( approximately 86%) of neurons are late-spiking (LS) cells, which can delay the onset of their spike trains by several seconds or more relative to the onset of a depolarizing current step. LS neurons previously have been shown to exist only in very small numbers in a limited number of other cortical regions. Anatomical reconstructions have revealed that the LS neurons vary greatly in morphology, including both pyramidal and nonpyramidal cells. Another surprising physiological finding is the fact that single-spiking (SS) neurons are the second most common cell type ( approximately 7%). SS neurons issue only a single action potential even in response to extreme depolarization. They have been seen previously in the amygdala, but never in cortex. A third remarkable finding is that there are almost no regular spiking (RS) neurons, unlike all other cortical regions that have been studied. This unique abundance of LS neurons in layer VI, along with the presence of SS neurons and the absence of RS neurons, demonstrates that layer VI of PR is unlike any other cortical region that has been studied to date.

Action Potentials↗
PubMed2001

Amygdalar nmda receptors are critical for the expression of multiple conditioned fear responses.

There is conflicting evidence regarding the issue of whether NMDA receptors in the basolateral amygdalar complex (BLA) are critically involved in the expression of conditioned fear. This matter was addressed by infusing the rat BLA with d,l-2-amino-5-phosphonovaleric acid (APV), a competitive NMDA receptor antagonist. APV infusion into the BLA was reported to block the expression of conditioned fear when measured by freezing but not when measured by fear-potentiated startle response to a loud noise. To examine this issue further, here we used multiple indices of conditioned fear, including analgesia, 22 kHz ultrasonic vocalization (USV), defecation, and freezing. Rats with bilateral BLA cannula implants underwent fear conditioning consisting of 10 tone-footshock pairings. Before context and tone fear-retention tests, animals received intra-BLA infusions with APV (2.5 microg/side) or artificial CSF. Both tone and context tests demonstrated that the expression of conditioned freezing, USV, defecation, and analgesia were significantly impaired by intra-amygdalar infusions of APV. In a second set of experiments, intra-BLA infusions of APV markedly impaired the normal expression of postshock fear responses during training, as measured by freezing, USV, and defecation. Immediate postshock fear expression was predictive of subsequent fear retention to the tone and context when the animals were not infused. These results are consistent with the hypothesis that amygdalar NMDA receptors participate in normal synaptic transmission and therefore the overall functioning of the amygdala.

2-Amino-5-phosphonovalerate↗
PubMed2001

Amygdala lesions block conditioned enhancement of the early component of the rat eyeblink reflex.

A tone conditioned stimulus (CS) previously paired with a grid shock unconditioned stimulus (US) can greatly enhance the early electromyographic (EMG) component (R1) of the rat eyeblink reflex. The hypothesis that the central nucleus of the amygdala (ACe) is an essential part of the circuitry mediating conditioned R1 enhancement was tested. After bilateral ACe lesions (L) or a sham operation (S), rats received paired presentations of the CS and US (P) or explicitly unpaired CS and US presentations (U), resulting in 4 groups: P/S, P/L, U/S, and U/L. ACe lesions completely prevented conditioned R1 enhancement, which was only exhibited in Group P/S. In the latter group, the "preextinction" conditioned enhancement effect was roughly a 2-fold increase in the R1 magnitude. Circuit-level mechanisms are discussed, and some advantages of the eyeblink EMG response in this general conditioning paradigm are considered.

Acoustic Stimulation↗
PubMed2000

Prolonged synaptic integration in perirhinal cortical neurons.

Layer II/III of rat perirhinal cortex (PR) contains numerous late-spiking (LS) pyramidal neurons. When injected with a depolarizing current step, these LS cells typically delay spiking for one or more seconds from the onset of the current step and then sustain firing for the duration of the step. This pattern of delayed and sustained firing suggested a specific computational role for LS cells in temporal learning. This hypothesis predicts and requires that some layer II/III neurons should also exhibit delayed and sustained spiking in response to a train of excitatory synaptic inputs. Here we tested this prediction using visually guided, whole cell recordings from rat PR brain slices. Most LS cells (19 of 26) exhibited delayed spiking to synaptic stimulation (>1 s latency from the train onset), and the majority of these cells (13 of 19) also showed sustained firing that persisted for the duration of the synaptic train (5-10 s duration). Delayed and sustained firing in response to long synaptic trains has not been previously reported in vertebrate neurons. The data are consistent with our model that a circuit containing late spiking neurons can be used for encoding long time intervals during associative learning.

Animals↗
PubMed2000

Endoscopic ultrasound in the staging of tumours of the oesophagus and gastro-oesophageal junction.

BACKGROUND: Modern management of upper gastro-intestinal cancer demands accurate pre-operative staging. In continental Europe and Japan, endoscopic ultrasound (EUS) is established as the investigation of choice for local staging of these cancers, but British experience with this technique is limited. METHODS: A retrospective review of the medical records of patients with oesophageal or gastro-oesophageal junction tumours during our first 3.5 years' experience with EUS was undertaken and the findings at EUS correlated with the pathology of the resected specimen. RESULTS: A total of 124 patients (86 males), with a mean age of 64.5 years, underwent EUS: 84 had adenocarcinoma and 26 squamous cell carcinoma. There were 3 failed EUS examinations, 42 patients did not have surgery for a variety of reasons, and 10 patients had pre-operative chemoradiotherapy. In the remaining 69 patients, correlation for T stage showed an accuracy of EUS of 80% and for N staging of 54% overall. Comparison of the initial 2 years with the final 18 months showed no change in the T staging accuracy but an improvement in the N staging accuracy from 50% to 60%. CONCLUSION: Once initial experience has been gained, EUS is an accurate procedure for T and N staging of tumours of the oesophagus and gastro-oesophageal junction. It should be included with other imaging modalities, such as CT scanning, in the pre-operative assessment of these tumours.

Adenocarcinoma↗
PubMed1999

Morphology and physiology of neurons in the rat perirhinal-lateral amygdala area.

Neuronal structure-function relationships were studied in rat brain slices containing the perirhinal cortex (PR) and immediately adjacent lateral nucleus of the amygdala (ALa). Using video microscopy, whole-cell recordings were made from visually preselected neurons that were labeled with biocytin for subsequent anatomical reconstructions. Most cells were 1 of 4 primary neurophysiological types: fast-spiking (FS), regular-spiking (RS), late-spiking (LS), and burst-spiking (BS). Fast-spiking neurons (small somata) were found throughout PR; RS neurons (stellates and pyramids) were present from layer II/III through VI of PR; BS neurons (large pyramids with thick nonbifurcating apical dendrites) were found in layer Va of PR; and LS neurons (stellates, small pyramids, and cone cells) were encountered in layers II/III and VI of PR. One subpopulation of LS neurons (small pyramids) was found in layer II/III; another (cone cells) was found in clusters spanning layer VI through the lateral portion of ALa. Layer Va also contained large RS pyramidal neurons whose axons were seen traveling in the external capsule, but not entering the ALa. Conversely, the axons of large RS pyramidal neurons in layer Vb typically projected deep into the ALa. The four primary firing patterns were present in ALa, which also contained irregular-spiking, slow-charging, and single-spiking cells. Spontaneous synaptic currents differed markedly among cell types and layers. There was excellent agreement between somatic areas measured from video images of living neurons and somatic areas from the same neurons following fixation. Representative montages, which combined the cellular neuroanatomy and neurophysiology, suggested a circuit-level organization that helps elucidate information processing through the PR-ALa region.

Amygdala↗
PubMed1999

Testing the fit of a quantal model of neurotransmission.

Many studies of synaptic transmission have assumed a parametric model to estimate the mean quantal content and size or the effect upon them of manipulations such as the induction of long-term potentiation. Classical tests of fit usually assume that model parameters have been selected independently of the data. Therefore, their use is problematic after parameters have been estimated. We hypothesized that Monte Carlo (MC) simulations of a quantal model could provide a table of parameter-independent critical values with which to test the fit after parameter estimation, emulating Lilliefors's tests. However, when we tested this hypothesis within a conventional quantal model, the empirical distributions of two conventional goodness-of-fit statistics were affected by the values of the quantal parameters, falsifying the hypothesis. Notably, the tests' critical values increased when the combined variances of the noise and quantal-size distributions were reduced, increasing the distinctness of quantal peaks. Our results support two conclusions. First, tests that use a predetermined critical value to assess the fit of a quantal model after parameter estimation may operate at a differing unknown level of significance for each experiment. Second, a MC test enables a valid assessment of the fit of a quantal model after parameter estimation.

Animals↗
PubMed1998

Methods for whole-cell recording from visually preselected neurons of perirhinal cortex in brain slices from young and aging rats.

This manuscript describes methods for preparing, visualizing, and recording from healthy perirhinal cortex neurons in brain slices from young and aging rats. We focused on perirhinal cortex because of its role in learning, memory, and aging-related cognitive decline. Detailed accounts of our dissection procedures are reported. Procedures that reliably yielded healthy neurons from juvenile rats were not conducive to obtaining healthy, readily-patchable neurons from aging rats, suggesting a procedure-by-age interaction. Performing an intracardiac perfusion, using a temperature-controlled vibratome, matching osmolarity between the cutting and incubation saline, using a slow cutting speed, and incubating slices at a warm temperature for 30 min were important when working with older tissue. Excellent visualization of neurons at depths of up to 100 microm was achieved in slices from all ages (without tissue clearing) avoiding the need to record from surface neurons, which are more likely to have truncated processes. Whole-cell recordings typically remained stable for several hours in neurons prepared from rats at all ages. These procedures should benefit neuroscientists interested in applying visually-guided whole-cell patch-clamp techniques to brain slice experiments using aged tissue. These methods should also facilitate the application of fluorescent imaging technology to brain slices for studying aging-related changes.

Age Factors↗
PubMed1998

Complex synaptic current waveforms evoked in hippocampal pyramidal neurons by extracellular stimulation of dentate gyrus.

Excitatory postsynaptic currents (EPSCs) evoked in hippocampal CA3 pyramidal neurons by extracellular stimulation of the dentate gyrus typically exhibit complex waveforms. They commonly have inflections or notches on the rising phase; the decay phase may exhibit notches or other obvious departures from a simple monoexponential decline; they often display considerable variability in the latency from stimulation to the peak current; and the rise times tend to be long. One hypothesis is that these complex EPSC waveforms might result from excitation via other CA3 pyramidal cells that were recruited antidromically or trans-synaptically by the stimulus due to the complex anatomy of this region. An alternative hypothesis is that EPSC complexity does not emerge from the functional anatomy but rather reflects an unusual physiological property, intrinsic to excitation-secretion coupling in mossy-fiber (mf) synaptic terminals, that causes asynchronous quantal release. We evaluated certain predictions of our anatomic hypothesis by adding a pharmacological agent to the normal bathing medium that should suppress di- or polysynaptic responses. For this purpose we used baclofen (3 microM), a selective agonist for the gamma-aminobutyric acid B receptor. The idea was that baclophen should discriminate against polysynaptic versus monosynaptic inputs by hyperpolarizing the cells, bringing them further from spike threshold and possibly also through inhibitory presynaptic actions. Whole cell recordings were done from visually preselected CA3 pyramidal neurons and EPSCs were evoked by fine bipolar electrodes positioned into the granule cell layer of the dentate. To the extent that the EPSC complexity reflects di- or polysynaptic responses, we predicted baclofen to reduce the number of notches on the rising and decay phases, reduce the variance in latency to peak of the EPSCs, decrease the amplitudes and rise times of the individual and averaged EPSCs, and increase the apparent failures in evoked EPSCs. All of these predictions were confirmed, in support of the hypothesis that these complex EPSC waveforms commonly reflect di- or polysynaptic responses. We also documented a distinctly different, intermittent, form of EPSC complexity, which also is predicted and easily explained by our anatomic hypothesis. In particular, the results were in accord with the suggestion that stimulation of the dentate gyrus might antidromically stimulate axon collaterals of CA3 neurons that make recurrent synapses onto the recorded cell. We conclude that the overall pattern of results is consistent with expectations based on the functional anatomy. The explanation does not demand a special type of intrinsic asynchronous mechanism for excitation-secretion coupling in the mf synapses.

Action Potentials↗
PubMed1997

Identification and characterization of rat orbicularis oculi motoneurons using confocal laser scanning microscopy.

The eyeblink reflex is one of the most extensively studied behaviors in mammals. The active downward force that causes lid closure is controlled by the orbicularis oculi (OO) muscle. To augment our studies on the neurophysiology and plasticity of the rat eyeblink circuit, here we present the first anatomical paper to focus exclusively on identifying and characterizing the OO motoneurons of the rat facial motor nucleus (FMN). One thousand and twenty-nine cells from four animals were retrogradely labeled by injecting the OO muscle with HRP and were imaged conventionally. One hundred and one cells from five animals were labeled by injecting the OO muscle with a 3000 mol. wt. fluorescent dextran and were imaged using confocal laser scanning microscopy (CLSM). The latter method resulted in little tissue shrinkage, bright labeling, and excellent resolution of the soma, dendrites, and axon. Furthermore, it is a histologically simple alternative to HRP for retrograde labeling from the neuromuscular junction. Both methods revealed that the OO motoneurons were distributed over the entire length of the FMN, that they were concentrated along the dorsal crest of the nucleus, and that they were less numerous in the extreme rostral and caudal regions. As measured using the CLSM method, cell body areas were highly variable, ranging from 317 to 1500 microm2, but there was no size gradient along the rostrocaudal extent of the FMN. The neurons exhibited seven primary dendrites on average, which gave rise to bifurcating and even trifurcating secondary dendrites. Using the HRP method, the estimated area of OO motoneurons ranged from 161 to 1381 microm2. The combined methods furnished a detailed characterization of the number, spatial distribution, and morphology of rat OO motoneurons. Moreover, these methods provide a useful way to analyze the circuitry that modulates the rat eyeblink.

Animals↗
PubMed1997

The effects of SB 206284A, a novel neuronal calcium-channel antagonist, in models of cerebral ischemia.

The effects of SB 206284A, 1-[7-(4-benzyloxyphenoxy)heptyl] piperidine hydrochloride, have been investigated in vitro on calcium and sodium currents in rat-cultured dorsal root ganglion (DRG) neurones and potassium-mediated calcium influx in rat synaptosomes. Cardiovascular hemodynamic effects in both anesthetized and conscious rats, and neuroprotective activity in in vivo cerebral ischemia models were also investigated. In the rat DRG cells, SB 206284A caused almost complete block of the sustained inward Ca2+ current (IC50 = 2.4 microM), suggesting that the compound is an effective blocker of slowly inactivating, high-voltage calcium current. SB 206284A reduced locomotor hyperactivity in the gerbil bilateral carotid artery occlusion model without affecting ischemia-induced damage in the hippocampal CA1 region. In the rat middle cerebral artery occlusion model, SB 206284A reduced lesion volume in the posterior forebrain, and in the rat photochemical cortical lesion model, lesion volume was reduced even when treatment was delayed until 4 hours after occlusion. At neuroprotective doses, SB 206284A had no cardiovascular effects. These findings show that SB 206284A is a novel calcium channel antagonist that shows neuroprotective properties.

Animals↗
PubMed1997

Calcium dynamics in thorny excrescences of CA3 pyramidal neurons.

Confocal laser scanning microscopy was used to visualize Ca2+ transients in a particular type of dendritic spine, known as a thorny excrescence, in hippocampal CA3 pyramidal neurons. These large excrescences or thorns, which serve as the postsynaptic target for the mossy-fiber synaptic inputs, were identified on the basis of their location, frequency, and size. Whole cell recordings were made from superficial CA3 pyramidal neurons in thick hippocampal slices with the use of infrared video microscopy; cells with proximal apical dendrites close to the surface of the slice were selected. Changes in intracellular Ca2+ levels were monitored by imaging changes in fluorescence of the dyes Calcium Green-1 and Fluo-3. Dual-emission fluorescence imaging was also employed with the use of a combination of Fluo-3 and the Ca2+-insensitive dye seminaphthorhodafluor-1. This method was used to decrease the potential influence of background fluorescence on the calculated changes in intracellular Ca2+ concentration ([Ca2+]i). Somatic depolarization produced increases in [Ca2+]i in both the thorn and the immediately adjacent dendrite. Changes in [Ca2+]i were time locked with the onset of depolarization and the decay began immediately after the termination of depolarization. The peak increase in the Ca2+ signal was significantly greater in the thorns than in the adjacent dendritic shafts. With the use of high-temporal-resolution methods (line scans), differences were also seen in the time course of Ca2+ signals in these two regions. The decay time constants of the Ca2+ signal were faster in thorns than in the adjacent dendritic shafts. These observations suggest that voltage-gated Ca2+ channels are localized directly on the dendritic spines receiving mossy-fiber input. Furthermore, Ca2+ homeostasis within thorny excrescences is distinct from Ca2+ regulation in the dendritic shaft, at least over brief time periods, a finding that could have important implications for synaptic plasticity and signaling.

Animals↗
PubMed1997

Comparative electrotonic analysis of three classes of rat hippocampal neurons.

We present a comparative analysis of electrotonus in the three classes of principal neurons in rat hippocampus: pyramidal cells of the CA1 and CA3c fields of the hippocampus proper, and granule cells of the dentate gyrus. This analysis used the electrotonic transform, which combines anatomic and biophysical data to map neuronal anatomy into electrotonic space, where physical distance between points is replaced by the logarithm of voltage attenuation (log A). The transforms were rendered as "neuromorphic figures" by redrawing the cell with branch lengths proportional to log A along each branch. We also used plots of log A versus anatomic distance from the soma; these reveal features that are otherwise less apparent and facilitate comparisons between dendritic fields of different cells. Transforms were always larger for voltage spreading toward the soma (V(in)) than away from it (V(out)). Most of the electrotonic length in V(out) transforms was along proximal large diameter branches where signal loss for somatofugal voltage spread is greatest. In V(in) transforms, more of the length was in thin distal branches, indicating a steep voltage gradient for signals propagating toward the soma. All transforms lengthened substantially with increasing frequency. CA1 neurons were electrotonically significantly larger than CA3c neurons. Their V(out) transforms displayed one primary apical dendrite, which bifurcated in some cases, whereas CA3c cell transforms exhibited multiple apical branches. In both cell classes, basilar dendrite V(out) transforms were small, indicating that somatic potentials reached their distal ends with little attenuation. However, for somatopetal voltage spread, attenuation along the basilar and apical dendrites was comparable, so the V(in) transforms of these dendritic fields were nearly equal in extent. Granule cells were physically and electrotonically most compact. Their V(out) transforms at 0 Hz were very small, indicating near isopotentiality at DC and low frequencies. These transforms resembled those of the basilar dendrites of CA1 and CA3c pyramidal cells. This raises the possibility of similar functional or computational roles for these dendritic fields. Interpreting the anatomic distribution of thorny excrescences on CA3 pyramidal neurons with this approach indicates that synaptic currents generated by some mossy fiber inputs may be recorded accurately by a somatic patch clamp, providing that strict criteria on their time course are satisfied. Similar accuracy may not be achievable in somatic recordings of Schaffer collateral synapses onto CA1 pyramidal cells in light of the anatomic and biophysical properties of these neurons and the spatial distribution of synapses.

Algorithms↗
PubMed1996

Conditioned enhancement of the early component of the rat eyeblink reflex.

Conditioned enhancement of the rat eyeblink reflex was studied using as a response measure the electromyogram (EMG) in the orbicularis oculi (oo) muscle, which is responsible for the active force generating eyelid closure. During a reflex eyeblink, the EMG evidences both a short-latency (R1) and a long-latency (R2) component, mediated by different circuits. The R2 response exhibits several experience- or use-dependent modifications. We were interested in the modifiability of the neurophysiologically simpler R1 response. Experiments were designed to determine whether the R1 response can be enhanced by a conditioned stimulus (CS) that has been explicitly paired with an aversive unconditioned stimulus (US). The R1 response was elicited by electrical stimulation of the supraorbital branch of the trigeminal nerve. Following long-delay conditioning, the CS produced a significant R1 enhancement and latency decrease that were dependent upon explicit CS-US pairings. The CS by itself produced no significant EMG response, consistent with a modulatory rather than additive effect. This is the first demonstration that the R1 response can be associatively modulated. Based on other evidence, we hypothesize that the CS-produced enhancement results from a relatively direct projection from the amygdala to the R1 circuit. As an index of aversive conditioning, R1 enhancement may prove to be a useful expression system because it offers high temporal resolution and the underlying circuitry is relatively simple-the shortest path from the fifth nerve to the muscle consisting of only two central synapses.

Animals↗