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G J Quirk

Publications and source records attributed to G J Quirk.

At least 19 recordsLinked to original sources
PubMed2001

Consolidation of extinction learning involves transfer from NMDA-independent to NMDA-dependent memory.

Extinction of conditioned fear to a tone paired with foot shock is thought to involve the formation of new memory. In support of this, previous studies have shown that extinction of conditioned fear depends on NMDA receptor-mediated plasticity. To further investigate the role of NMDA receptors in extinction, we examined the effects of the NMDA antagonist d(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) on the extinction of conditioned freezing and suppression of bar pressing (conditioned emotional response). Rats extinguished normally during a 90 min session in the presence of systemic CPP (10 mg/kg), but were unable to recall extinction learning 24 hr later. This suggests that an NMDA-independent form of plasticity supports short-term extinction memory, but NMDA receptors are required for consolidation processes leading to long-term extinction memory. Surprisingly, extinction learned in the presence of CPP was recalled normally when tested 48 hr after training, suggesting a delayed consolidation process that was able to improve memory in the absence of further training. Delayed consolidation involves NMDA receptors because CPP injected on the rest day between training and test prevented 48 hr recall of extinction learned under CPP. Control experiments showed that the effect of CPP on memory consolidation was not caused by state-dependent learning or reduced expression of freezing under CPP. These findings demonstrate that NMDA receptor activation is critical for consolidation of extinction learning and that this process can be initiated after training has taken place. We suggest that consolidation of extinction involves off-line relearning that reinforces extinction memory through NMDA-mediated plasticity, perhaps in prefrontal-amygdala circuits.

Amygdala↗
PubMed2000

The role of ventromedial prefrontal cortex in the recovery of extinguished fear.

Conditioned fear responses to a tone paired with footshock extinguish when the tone is presented repeatedly in the absence of shock. Rather than erase the tone-shock association, extinction is thought to involve new learning accompanied by inhibition of conditioned responding. Despite much interest in extinction from a clinical perspective, little is known about the neural circuits that are involved. Although the prefrontal cortex has a well established role in the inhibition of inappropriate behaviors, previous reports have disagreed as to the role of the ventromedial prefrontal cortex (vmPFC) in extinction. We have reexamined the effects of electrolytic vmPFC lesions made before training on the acquisition, extinction, and recovery of conditioned fear responses in a 2 d experiment. On Day 1 vmPFC lesions had no effect on acquisition or extinction of conditioned freezing and suppression of bar pressing. On Day 2 sham rats recovered only 27% of their acquired freezing, whereas vmPFC-lesioned rats recovered 86%, which was indistinguishable from a control group that never received extinction. The high recovery in lesioned rats could not be attributed to decreased motivation or altered sensitivity to footshock. vmPFC lesions that spared the caudal infralimbic (IL) nucleus had no effect. Thus, the vmPFC (particularly the IL nucleus) is not necessary for expression of extinction, but it is necessary for the recall of extinction learning after a long delay. These data suggest a role of the vmPFC in consolidation of extinction learning or the recall of contexts in which extinction took place.

Animals↗
PubMed1998

Differential effects of amygdala lesions on early and late plastic components of auditory cortex spike trains during fear conditioning.

In auditory fear conditioning, pairing of a neutral acoustic conditioned stimulus (CS) with an aversive unconditioned stimulus (US) results in an enhancement of neural responses to the CS in the amygdala and auditory cortex. It is not clear, however, whether cortical plasticity governs neural changes in the amygdala or vice versa, or whether learning in these two structures is determined by independent processes. We examined this issue by recording single-cell activity in the auditory cortex (areas Te1, Te1v, and Te3) of freely behaving, amygdalectomized rats using a movable bundle of microwires. Amygdala damage did not affect short-latency (0-50 msec) tone responses, nor did it interfere with conditioning-induced increases of these onset responses. In contrast, lesions of the amygdala interfered with the development of late (500-1500 msec) conditioned tone responses that were not present before conditioning. Furthermore, whereas onset conditioned responses in the control group remained elevated after 30 extinction trials (presentation of CS alone), onset responses in lesioned animals returned to their preconditioning firing level after approximately 10 extinction trials. These results suggest that the amygdala enables the development of long-latency (US anticipatory) responses and prevents the extinction of short-latency onset responses to threatening stimuli. The findings further suggest that auditory cortex cells may participate differently in explicit and implicit memory networks.

Acoustic Stimulation↗
PubMed1998

Central somatosensory conduction time in severely growth-stunted children.

To examine the effects of chronic malnutrition on central nervous system function, we used the somatosensory evoked potential to measure the central conduction time of 20 children aged 7-8 y with heights below the third percentile for their age and 20 control children in Honduras. The two groups differed significantly in socioeconomic status, achievement in Bender's neurointegrative test, and hematocrit, but not in birth weight. After median nerve stimulation, the mean central conduction time (interpeak latency between N13 and N20) for the growth-stunted group (6.19 +/- 0.52 ms) did not differ significantly from that of the control subjects (6.30 +/- 0.58 ms), suggesting appropriate myelination and fiber diameter. Somatosensory tracts may escape damage resulting from postnatal dietary deficiencies because myelination in these tracts is almost complete at birth.

Central Nervous System↗
PubMed1997

Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala.

Single neurons were recorded in freely behaving rats during fear conditioning from areas of auditory cortex that project to the lateral nucleus of the amygdala (LA). The latency and rate of conditioning and extinction were analyzed, and the results were compared to previous recordings from LA itself. Auditory cortex neurons took more trials to learn, and they responded more slowly than LA neurons within trials. Short-latency plasticity in LA, therefore, reflects inputs from the auditory thalamus rather than the auditory cortex. Unlike LA cells, some auditory cortex cells showed late conditioned responses that seemed to anticipate the unconditioned stimulus, while others showed extinction-resistant memory storage. Thus, rapid conditioning of fear responses to potentially dangerous stimuli depends on plasticity in the amygdala, while cortical areas may be particularly involved in higher cognitive (mnemonic and attentional) processing of fear experiences.

Acoustic Stimulation↗
PubMed1995

Early malnutrition followed by nutritional restoration lowers the conduction velocity and excitability of the corticospinal tract.

The physiological sequelae of undernutrition were investigated in rats that were undernourished from day 1-21 and subsequently free-fed to 75 days of age. Population responses were recorded in the corticospinal tract following surface stimulation of the motor cortex, which activates corticospinal cells directly, and also indirectly via cortical synapses. The conduction velocity of the fastest corticospinal fibers in 15 malnourished rats was 16.9 m/s, significantly slower (P < 0.001) than the 20.0 m/s observed in 26 controls. In addition, the excitability of corticospinal neurons to direct stimulation was reduced as much as 67% in malnourished rats, while no effect on synaptic activation was observed. Our findings suggest that early malnutrition reduces the number of large fibers in the adult corticospinal tract. These results are discussed with respect to known morphological and behavioral effects of malnutrition in rats and their relevance to humans.

Analysis of Variance↗
PubMed1995

Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat.

The lateral nucleus of the amygdala (LA) is the first site in the amygdala where the plasticity underlying fear conditioning could occur. We simultaneously recorded from multiple LA neurons in freely moving rats during fear conditioning trials in which tones were paired with foot shocks. Conditioning significantly increased the magnitude of tone-elicited responses (often within the first several trials), converted unresponsive cells into tone-responsive ones, and altered functional couplings between LA neurons. The effects of conditioning were greatest on the shortest latency (less than 15 ms) components of the tone-elicited responses, consistent with the hypothesis that direct projections from the auditory thalamus to LA are an important link in the circuitry through which rapid behavioral responses are controlled in the presence of conditioned fear stimuli.

Acoustic Stimulation↗
PubMed1995

Starting a neuroscience research laboratory in a developing country: a Fulbright experience in Honduras.

The first laboratory of neurophysiology was installed in the medical school of the University of Honduras during the 1992-1993 academic year. The goal of the project was to improve the teaching of physiology in the medical curriculum and to establish a neuroscience research laboratory able to address Honduran needs. In addition to a computer learning facility and wet labs in neurophysiology for medical students, an independent research program that focused on social problems in the country (for example, the effects of malnutrition on the developing central nervous system) was developed, paving the way for the first graduate program in physiology in Honduras. Funded by a Fulbright Lectureship Grant, the shoe-string budget was augmented by donations of equipment by colleagues. This first-hand account describes the planning and implementation of the project, covering both expected and unexpected problems and successes. An update on the progress of the lab after two years of independent operation is also described.

Budgets↗
PubMed1994

Stress disorders of families of the disappeared: a controlled study in Honduras.

The effect of forced disappearance on the physical and psychological health of family members was assessed by interviews carried out in Honduras. Families of the disappeared were compared with two control groups: (1) families who lost a member due to accident or illness; and (2) families where no one had died within the past 10 years. Constellations of stress-related symptoms commonly seen in post-traumatic stress disorder and other anxiety disorders were approx. 2 times more prevalent in families of the disappeared as compared to the other two groups, indicating that families of the disappeared suffer over and above that due to normal grieving. It is suggested that the atmosphere of fear and isolation experienced by families of the disappeared is a causative factor in the prolongation of stress-related disorders years after the traumatic event.

Adaptation, Psychological↗
PubMed1992

Firing relations of medial entorhinal neurons to the hippocampal theta rhythm in urethane anesthetized and walking rats.

The firing of neurons from layers II and III of medial entorhinal cortex (MEC) was examined in relation to the hippocampal theta rhythm in urethane anesthetized and walking rats. 1) MEC neurons showed a significant phase relation to the hippocampal theta rhythm in both walking and urethane anesthetized rats, suggesting that this region contributes to the generation of both atropine-resistant and atropine-sensitive theta rhythm components. 2) The proportion of phase-locked cells was three times greater in walking rats (22/23 cells) as compared to anesthetized rats (8/23 cells), indicating that MEC cells made a greater contribution during walking theta rhythm. This difference was also manifest in the greater mean vector length for the group of phase-locked MEC cells during walking: 0.39 +/- 0.13 versus 0.21 +/- 0.08. Firing rate differences between walking and urethane conditions were not significant. 3) In walking rats, MEC cells fired on the positive peak of the dentate theta rhythm (group mean phase = 5 degrees; 0 degrees = positive peak at the hippocampal fissure). This is close to the reported phases for dentate granule and hippocampal pyramidal cells. The distribution of MEC cell phases in urethane anesthetized rats was broader (group mean phase = 90 degrees), consistent with the phase data reported for hippocampal projection cells. These findings suggest that medial entorhinal neurons are the principal determinant of theta-related firing of hippocampal neurons and that their robust rhythmicity in walking as compared to urethane anesthesia accounts for EEG differences across the two conditions.

Anesthesia↗
PubMed1992

The positional firing properties of medial entorhinal neurons: description and comparison with hippocampal place cells.

Hippocampal place cells in the rat are so named because they fire predominantly within circumscribed regions of the environment. This study describes the positional firing properties of cells afferent to hippocampal place cells, in superficial layers of medial entorhinal cortex (MEC). MEC cells in these layers project to the hippocampus via the perforant path and, along with lateral entorhinal cells, are the sole route by which cortical information reaches the hippocampus. MEC cells were recorded from rats while they retrieved pellets in simple geometric enclosures. The behavioral task as well as procedures for data collection and analysis were the same used in previous studies on hippocampal place cells (e.g., Muller et al., 1987) in order to facilitate the direct comparison between hippocampal and entorhinal cells. The firing patterns of MEC cells show pronounced locational variations reminiscent of hippocampal firing fields, but with a lower signal-to-noise ratio. While noisy, MEC firing patterns are stationary in time as evidenced by their reproducibility, and the improvement in spatial signal with long-duration recordings. Furthermore, MEC firing patterns are not due to variations in the rat's behavior. Taken together, these data show that the positional firing variations in MEC cells are due to the location-specificity of MEC cells. These and additional data lead us to conclude that location-specific information exists prior to the hippocampus. MEC cells are similar to hippocampal place cells in that their firing can be controlled by the rotation of a visual cue (a white card attached to the wall), but is not disrupted by removing the cue. An important difference between hippocampal and entorhinal cells was seen when the shape of the recording chamber was changed. In the transition from a cylinder to an equal-area square of similar appearance, MEC firing patterns topologically transformed (or "stretched") while those of hippocampal place cells changed to an unpredictable pattern. We conclude that the positional firing of MEC cells is more "sensory bound" than hippocampal cells, and that the ability to discriminate different environments, while present in the hippocampus, is not yet present in its input from MEC.

Animals↗
PubMed1990

Corticospinal responses to electrical stimulation of motor cortex in the rat.

Direct and indirect corticospinal responses to electrical stimulation of motor cortex were identified in urethane-anesthetized rats. 'Killed-end' recordings were taken from the corticospinal tract at the level of the cervical cord (C1-C2) and from the medullary pyramid. The identities of direct (D) and indirect (I) corticospinal responses were confirmed by: (1) removing motor cortex to eliminate I activity, and (2) pharmacologically increasing neocortical excitability, prior to any lesions, to increase I activity. Our data indicate that the conduction velocity of the fastest corticospinal fibers is approximately 18 m/s. Our identification of the components of the corticospinal response will permit the interpretation of the more complicated surface or 'non-killed-end' depth recordings which have shown particular utility in evaluating spinal cord damage.

Action Potentials↗
PubMed1990

The firing of hippocampal place cells in the dark depends on the rat's recent experience.

Hippocampal "place cells" fire when a freely moving rat is in a given location. The firing of these cells is controlled by visual and nonvisual environmental cues. The effects of darkness on the firing of place cells was studied using the task of Muller et al. (1987), in which rats were trained to chase randomly scattered food pellets in a cylindrical drum with a white cue-card attached to the wall. The position of the rats was tracked via an infrared LED on the headstage with a video system linked to computer. Two experimental protocols were used: in the first, lights were turned off after the rat had already been placed in the chamber; in the second, the rat was placed in the darkened chamber. The dark segments produced by these 2 methods were identical with respect to light and other cues but differed with respect to the rat's experience. The firing patterns of 24 of 28 cells were unaffected by darkness when it was preceded by a light period. In contrast, the firing patterns of 14 of 22 cells changed dramatically when the rats were put into the darkened chamber. Furthermore, the majority of cells that changed their firing pattern in initial darkness maintained that change when the lights were turned on. These results show that place cells can fire differently in identical cue situations and that the best predictor of firing pattern is a combination of current cues and the rat's recent experience. The results are discussed in terms of mnemonic properties of hippocampal cells and "remapping" of place cell representations.

Animals↗
PubMed1987

Separable roles of hippocampal granule cells in forgetting and pyramidal cells in remembering spatial information.

To investigate the roles individual hippocampal cell groups play in processing of spatial information for memory, we administered low-intensity electrical stimulation to the granule cells, CA3 and CA1 pyramidal cells of the dorsal hippocampus at selected times before and after acquisition of the solution to a radial maze win-stay task. Stimulation of any of the 3 cells populations yielded a variable duration anterograde disruption of memory performance, while stimulation of dentate gyrus granule cells alone produced a declarative memory-specific retrograde amnesia. The amnestic effect of granule cell stimulation was not associated with after discharges in the hippocampus and was prevented by systemic administration of the opiate antagonist naloxone. Our results support the view that this electrical stimulus does not disrupt, but rather, activates the normal function of the granule cell system, resulting in erasure of information held in declarative memory. In contrast, similar activation of the pyramidal cell system does not yield retrograde amnesia, suggesting a normal role for these cells in promoting memory for spatial information.

Animals↗
PubMed1987

Physiological basis of motor effects of a transient stimulus to cerebral cortex.

This contribution includes a selective review of previously published material, findings from some new experiments, and discussion of some relationships between animal and recent human data. The major questions are: What descends from the cerebral cortex after a brief surface stimulus? What explains the various components of the corticofugal discharge? What are the motor consequences of the corticofugal discharge, and what are the effects of lesions on both? The focus is on the corticospinal system, which through its monosynaptic connection with alpha motoneurons of distal muscles accounts for the short latency movements after a transient cortical stimulus. The pyramidal and lateral corticospinal tract response in monkey or cat to a surface stimulus applied to area 4 is a direct (D) wave conducted in fast axons followed by several indirect (I) waves with a period of greater than 1 ms. Although computer summing reveals, at increasing amplitudes, D and I waves in recordings from nuchal skin, vertebra, and surface of the spinal cord, "killed end" recording is essential to reveal the true extent of I relative to D waves. The D wave might result from excitation of: the initial segment (IS), i.e., the classical spike trigger zone; the first or deeper nodes in white matter; or arborizations of the axon collaterals in gray matter. Under different circumstances, each of these modes of excitation can be effective. Thus, with threshold stimulation through separated bipolar electrodes, intracellular recording from pyramidal tract (PT) and uninvaded motor cortical neurons shows that D activation usually occurs when the membrane potential immediately before the stimulus is relatively depolarized, implying excitation of the IS region, i.e., close to the site of synaptic transfer. A monopolar surface (+) stimulus at the appropriate focus usually generates a D wave at weaker intensity than does a surface (-) stimulus. However, if a little above threshold, stimuli of either polarity generate both D and I waves, but the ratio of D:I amplitude is usually greater with surface (+) stimulation. A theoretical estimate of the depth of excitation by a surface (+) stimulus was consistent with threshold excitation occurring at the first node. Slow PT neurons are excited by surface stimulation, but trivially contribute to population PT or corticospinal recordings. Intracellular recording from PT neurons identifies a monosynaptic excitatory postsynaptic potential as the cause of the first I wave, the period between successive I waves reflecting single delays for synaptic discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗