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J R Moyer

Publications and source records attributed to J R Moyer.

17 recordsLinked to original sources
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↗
PubMed2000

Increased excitability of aged rabbit CA1 neurons after trace eyeblink conditioning.

Cellular properties of CA1 neurons were studied in hippocampal slices 24 hr after acquisition of trace eyeblink conditioning in young adult and aging rabbits. Aging rabbits required significantly more trials than young rabbits to reach a behavioral criterion of 60% conditioned responses in an 80 trial session. Intracellular recordings revealed that CA1 neurons from aging control rabbits had significantly larger, longer lasting postburst afterhyperpolarizations (AHPs) and greater spike frequency adaptation (accommodation) relative to those from young adult control rabbits. After learning, both young and aging CA1 neurons exhibited increased postsynaptic excitability compared with their respective age-matched control rabbits (naive and rabbits that failed to learn). Thus, after learning, CA1 neurons from both age groups had reduced postburst AHPs and reduced accommodation. No learning-related differences were seen in resting membrane potential, membrane time constant, neuron input resistance, or action potential characteristics. Furthermore, comparisons between CA1 neurons from trace-conditioned aging and trace-conditioned young adult rabbits revealed no statistically significant differences in postburst AHPs or accommodation, indicating that similar levels of postsynaptic excitability were attained during successful acquisition of trace eyeblink conditioning, regardless of rabbit age. These data represent the first in vitro demonstration of learning-related excitability changes in aging rabbit CA1 neurons and provide additional evidence for involvement of changes in postsynaptic excitability of CA1 neurons in both aging and learning.

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↗
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↗
PubMed1997

Enhanced synaptic transmission in CA1 hippocampus after eyeblink conditioning.

CA1 field potentials evoked by Schaffer collateral stimulation of hippocampal slices from trace-conditioned rabbits were compared with those from naive and pseudo-conditioned controls. Conditioned rabbits received 80 trace conditioning trials daily until reaching a criterion of 80% conditioned responses in a session. Hippocampal slices were prepared 1 or 24 h after reaching criterion (for trace-conditioned animals) or after a final unpaired stimulus session (for pseudo-conditioned animals); naive animals were untrained. Both somatic and dendritic field potentials were recorded in response to various stimulus durations. Recording and data reduction were performed blind to the conditioning state of the rabbit. The excitatory postsynaptic potential slope was greater in slices prepared from trace-conditioned animals killed 1 h after conditioning than in naive and pseudo-conditioned controls (repeated-measures analysis of variance, F = 4.250, P < 0.05). Associative learning specifically enhanced synaptic transmission between CA3 and CA1 immediately after training. This effect was not evident in the population field potential measured 24 h later.

Animals↗
PubMed1996

Trace eyeblink conditioning increases CA1 excitability in a transient and learning-specific manner.

Time-dependent, learning-related changes in hippocampal excitability were evaluated by recording from rabbit CA1 pyramidal neurons in slices prepared at various times after acquisition of trace eyeblink conditioning. Increased excitability (reduced postburst afterhyperpolarizations and reduced spike-frequency adaptation) was seen as early as 1 hr after acquisition to behavioral criterion, was maximal in neurons studied 24 hr later, and returned to baseline within 7 d, whereas behavioral performance remained asymptotic for months. Neurons were held at -67 mV to equate voltage-dependent effects. No learning-related effects were observed on input resistance, action-potential amplitude or duration, or resting membrane potential. The excitability changes were learning-specific, because they were not seen in neurons from very slow learning (exhibited < 30% conditioned responses after 15 training sessions) or from pseudoconditioned control rabbits. Neurons from rabbits that displayed asymptotic behavioral performance after long-term retention testing (an additional training session 14 d after learning) were also indistinguishable from control neurons. Thus, the increased excitability of CA1 neurons was not performance- or memory-dependent. Rather, the time course of increased excitability may represent a critical window during which learning-specific alterations in postsynaptic excitability of hippocampal neurons are important for consolidation of the learned association elsewhere in the brain.

Animals↗
PubMed1996

Calcium-dependent afterhyperpolarization and learning in young and aging hippocampus.

Hippocampally-dependent trace eyeblink conditioning has been shown to be affected by aging. Aging animals take more trials to acquire the association and are more likely to be unable to learn the task. Hippocampal neurons show decreased post-burst afterhyperpolarizations (AHPs) and less accomodation after conditioning, in a time-dependent fashion which may relate to the role of hippocampus in learning consolidation. CA1 neurons in aging rabbits show increased AHPs and more accomodation, i.e., they are less excitable, and larger calcium action potentials. These age-related changes may underlie the learning deficits in aging rabbits. The lipophylic calcium channel blocker nimodipine reduces the AHP, accomodation and calcium action potential at low concentrations in aging but not young CA1 neurons. Nimodipine also enhances learning rate in a variety of tasks, including eyeblink conditioning, in aging but not young animals and humans. Altered calcium handling by neurons of aging mammals is a striking change, is pharmacologically manipulable, and may be an important factor in altered learning and cognitive abilities in the aging.

Action Potentials↗
PubMed1996

Transient changes in excitability of rabbit CA3 neurons with a time course appropriate to support memory consolidation.

1. The excitability of CA3 pyramidal neurons was assessed with intracellular recordings in hippocampal slices from behaviorally naive rabbits. CA3 pyramidal neurons had large (-13.1 +/- 0.3 mV; mean +/- SE) postburst afterhyperpolarization (AHPs) and exhibited robust spike-frequency adaptation (accommodation) to prolonged (800-ms) depolarizing current injection at resting potentials of -68 mV. AHP and accommodation measures differed in scale but not in kind from those obtained in stable recordings from CA1 pyramidal neurons in the same slices or from the same rabbits, with CA3 neurons having larger longer AHPs but fewer spikes during accommodation. 2. Groups of rabbits were trained in a simple, associative-learning task, trace eye-blink conditioning, which required an intact hippocampus for successful acquisition. Memory consolidation in this task also involves the hippocampus, whereas long-term retention of the learned response does not. The time course and magnitude of learning-specific changes in excitability were assessed in 201 CA3 pyramidal neurons. 3. Learning increased the excitability of CA3 pyramidal neurons soon after acquisition (within 1-24 h). The mean postburst AHP was reduced to approximately half (-6.4 +/- 0.3 mV) the basal amplitude of the AHP observed in naive controls. The area and duration of the postburst AHP similarly were reduced. Approximately half of all pyramidal neurons tested soon after learning exhibited significantly reduced AHPs, whereas none exhibited enhanced AHPs. 4. Trace conditioning also reduced accommodation of CA3 pyramidal neurons 1-24 h after learning. Neurons from successfully trained rabbits fired significantly more action potentials (5.6 +/- 1.5) in response to prolonged depolarization than did neurons from naive controls (4.1 +/- 0.2). The magnitude of the learning-specific change in accommodation was less than that for the AHP. Approximately 45% of neurons tested exhibited significantly reduced accommodation soon after learning. 5. Both learning-specific changes in CA3 increased neuronal excitability. Both changes were highly time dependent. AHPs were reduced maximally 1-24 h after learning, then increased, returning to basal (naive) levels within 7 days and remaining basal thereafter. The decay rate of accommodation to basal levels preceded that of the AHP by several days. 6. Other membrane properties, including action potential characteristics, resting potential, and input resistance, were unchanged by learning. The restriction of the observed changes to two interrelated measures of excitability concurs with earlier reports that learning-specific changes in the mammalian hippocampus are linked to changes in a limited number of membrane conductances. 7. Learning, not long-term memory or performance of the learned behavior, was linked to the excitability changes. Neurons from rabbits that failed to acquire the task after considerable training exhibited no excitability changes. Neurons from pseudoconditioned rabbits were indistinguishable from neurons of behaviorally naive controls. Finally, neurons from rabbits that explicitly demonstrated long-term retention of the conditioned response were indistinguishable from those of naive controls. 8. Behavioral changes persisted for extremely long periods, but the observed changes in hippocampal excitability were transient and greatest soon after learning. Excitability was enhanced for a period of a few days, a period demonstrated in other eyeblink studies to be required for memory consolidation. Because hippocampal excitability then returned to basal levels but memory of the learned task persisted, postconsolidation memory traces (the "engram") must be extrahippocampal.

Action Potentials↗
PubMed1994

Nimodipine decreases calcium action potentials in rabbit hippocampal CA1 neurons in an age-dependent and concentration-dependent manner.

Intracellular recordings were made from rabbit hippocampal CA1 neurons in vitro using slices from aging and young adult rabbits. Calcium action potentials were studied in the presence of 4 microns tetrodotoxin using electrodes filled with 2M CsCl. Increasing concentrations of the dihydropyridine L-type calcium channel antagonist nimodipine were tested on the amplitude and time course of calcium action potentials. The calcium action potential (AP) consisted of two components: an initial fast phase followed by a slower plateau phase. No difference in the peak amplitude of the initial fast phase was observed between age groups. The amplitude and duration of the slower plateau phase of the calcium AP was significantly larger in aging neurons. Switching to a zero Ca2+ medium in the presence of 200 microns CdCl2 completely blocked the calcium AP. Nimodipine decreased the plateau phase of the calcium AP at concentrations as low as 100 nm in aging neurons and 10 microns in young neurons. Switching to higher concentrations of nimodipine did not reveal any substantially increased block of the calcium AP plateau phase. These data suggest that enhanced calcium influx through L-type calcium channels is largely responsible for the enhanced calcium action potentials observed in aging CA1 neurons. The action of nimodipine in reducing the plateau phase of the calcium action potential may underlie the drug's notable ability to improve learning in hippocampally dependent tasks in aging animals.

Action Potentials↗
PubMed1994

A system for quantitative analysis of associative learning. Part 1. Hardware interfaces with cross-species applications.

This paper describes a reliable, durable, and readily calibrated hardware interface system designed to present sensory stimuli at precise time intervals and to transduce and digitize behavioral data in classical conditioning experiments. It has been extensively tested in a 'model'-associative learning task, conditioning of eyeblink or nictitating membrane responses, but is readily adapted to other behavioral paradigms. Each system can run a pair of conditioned experimental or pseudoconditioned control subjects simultaneously, or collect data from a single subject carrying out two tasks simultaneously. The requirements of the system are defined, based around an inexpensive AT-class MS-DOS microcomputer. The interface hardware needed to present auditory tone conditioned stimuli and corneal airpuff-unconditioned stimuli to training subjects are detailed, with timing signals provided by TTL pulses generated at the digital output ports of an analog-to-digital (A/D) converter. An electronic circuit is described that provides stable inputs to the A/D converter, transducing eyeblink responses to voltage signals opto-electronically, without requiring any invasive attachment of the subject to the subject to the measuring device. The 1-piece eyeblink sensor used (selected for ease of alignment and maintenance) is also discussed. Examples of applications for classical conditioning of rabbits, rats, and human subjects are described. A companion paper describes data-acquisition and control software written as a user-friendly interface for this hardware system.

Animals↗
PubMed1993

Functional aspects of calcium-channel modulation.

Associative learning is accompanied by a number of changes in the brain, many mediated by calcium. We have used eyeblink conditioning, a well-controlled learning task in animals and humans, to elucidate these changes. Our studies have focused on the hippocampus, a temporal lobe structure known to be important for storage of new information during learning in mammalian brain. Hippocampal neurons show an enhanced firing rate during learning correlated with behavioral acquisition; they also show reduction in a calcium-mediated after-hyperpolarization (AHP), a likely mechanism for their enhanced activity. Aging animals and humans exhibit learning deficits; aging hippocampal neurons show increased AHPs and altered calcium buffering, which contribute to the behavioral learning deficits. Intravenous administration of the calcium antagonist nimodipine causes aging rabbits to learn the eyeblink conditioning task as quickly as young controls. Oral nimodipine enhances learning rates in aging rabbits, rats, and monkeys. In each case, the type of learning task analyzed is dependent on hippocampal processing for acquisition and is impaired with aging. Nimodipine also reverses aging-related alterations in open field behavior of both rats and rabbits. We have done a series of physiological studies focused on the possible role of nimodipine in enhancing neuronal activity in the hippocampus of aging rabbits. The purpose of these studies was to determine how nimodipine may be functioning at a cellular level to increase the learning rate. Four major conclusions may be drawn from our data: (a) Nimodipine strongly enhanced the firing rate of single hippocampal pyramidal neurons recorded in vivo in an aging- and concentration-dependent fashion. Other calcium-channel blockers, such as nifedipine and flunarizine, given to control for cerebral blood flow changes, had essentially no effect on the hippocampal firing rate. (b) The slow AHP, mediated by an outward calcium-activated potassium current, was markedly larger in pyramidal neurons in hippocampal slices prepared from aging rabbits. Nimodipine, at concentrations as low as 100 nM, reliably reduced the AHPs of aging pyramidal cells. Aging neurons also showed more spike frequency adaptation, or accommodation, than young neurons. Nimodipine partially blocked accommodation at concentrations as low as 10 nM in aging neurons. (c) The calcium action potential was larger in aging neurons. Nimodipine modulated the calcium action potential in an age- and concentration-dependent fashion; concentrations as low as 100 nM reduced the calcium action potential in aging CA1 neurons without effects on young cells. (d) Nimodipine blocked the high threshold, noninactivating calcium current (L-type calcium current) in acutely dissociated hippocampal pyramidal neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner.

1. Cellular properties were studied before and after bath application of the dihydropyridine L-type calcium channel antagonist nimodipine in aging and young rabbit hippocampal CA1 pyramidal cells in vitro. Various concentrations of nimodipine, ranging from 10 nM to 10 microM, were tested to investigate age- and concentration-dependent effects on cellular excitability. Drug studies were performed on a population of neurons at similar holding potentials to equate voltage-dependent effects. The properties studied under current-clamp conditions included steady-state current-voltage relations (I-V), the amplitude and integrated area of the postburst afterhyperpolarization (AHP), accommodation to a prolonged depolarizing current pulse (spike frequency adaptation), and single action-potential waveform characteristics following synaptic activation. 2. Numerous aging-related differences in cellular properties were noted. Aging hippocampal CA1 neurons exhibited significantly larger postburst AHPs (both the amplitude and the integrated area were enhanced). Aging CA1 neurons also exhibited more hyperpolarized resting membrane potentials with a concomitant decrease in input resistance. When cells were grouped to equate resting potentials, no differences in input resistance were noted, but the AHPs were still significantly larger in aging neurons. Aging CA1 neurons also fired fewer action potentials during a prolonged depolarizing current injection than young CA1 neurons. 3. Nimodipine decreased both the peak amplitude and the integrated area of the AHP in an age- and concentration-dependent manner. At concentrations as low as 100 nM, nimodipine significantly reduced the AHP in aging CA1 neurons. In young CA1 neurons, nimodipine decreased the AHP only at 10 microM. No effects on input resistance or action-potential characteristics were seen. 4. Nimodipine increased excitability in an age- and concentration-dependent manner by decreasing spike frequency accommodation (increasing the number of action potentials during prolonged depolarizing current injection). In aging CA1 neurons, this effect was significant at concentrations as low as 10 nM. In young CA1 neurons, nimodipine decreased accommodation only at higher concentrations (> or = 1.0 microM). 5. We conclude that aging CA1 neurons were less excitable than young neurons. In aging hippocampus, nimodipine restores excitability, as measured by size of the AHP and degree of accommodation, to levels closely resembling those of young adult CA1 neurons. These actions of nimodipine on aging CA1 hippocampal neurons may partly underlie the drug's notable ability to improve associative learning in aging rabbits and other mammals. Reversal of inhibitory postsynaptic potentials (IPSPs) by chloride ion and/or current injections into six motoneurons revealed the presence of inhibition during the period between phrenic bursts during fictive vomiting and also during the final phase of expulsion when phrenic discharge ceased by abdominal discharge continued. 3. Fictive coughing, evoked by repetitive electrical stimulation of superior laryngeal nerve afferents, was characterized by a large phrenic discharge followed immediately by a large abdominal nerve discharge. During fictive coughing, phrenic motoneurons retained their ramplike depolarizations throughout phrenic discharge; however, the amplitude of depolarization was greater than during inspiration. During the subsequent abdominal nerve discharge, the phrenic membrane potential usually underwent an initial rapid, transient hyperpolarization followed by a gradual repolarization associated with increased synaptic noise.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Hippocampectomy disrupts trace eye-blink conditioning in rabbits.

The role of the hippocampus (HPC) in trace eye-blink conditioning was evaluated using a 100-ms tone conditioned stimulus (CS), a 300- or 500-ms trace interval, and a 150-ms air puff unconditioned stimulus (UCS). Rabbits received complete hippocampectomy (dorsal & ventral), sham lesions, or neocortical lesions. Hippocampectomy produced differential effects in relation to the trace interval used. With a 300-ms trace interval, HPC-lesioned Ss showed profound resistance to extinction after acquisition. With a 500-ms trace interval, HPC-lesioned Ss did not learn the task (only 22% conditioned responses (CRs) after 25 sessions, whereas controls showed greater than 80% after 10 sessions), and on the few trials in which a CR occurred, most were "nonadaptive" short-latency CRs (i.e., they started during or just after the CS and always terminated prior to UCS onset). The authors conclude that the HPC encodes a temporal relationship between CS and UCS, and when the trace interval is long enough (e.g., 500 ms), that the HPC is necessary for associative learning of the conditioned eye-blink response.

Animals↗
PubMedDate not supplied

Dietary nimodipine improves associative learning in aging rabbits.

The effects of oral nimodipine on the acquisition of the conditioned eye-blink response in aging rabbits were examined. Three groups of rabbits were compared: young and aging controls fed NIH-09 rabbit chow and aging rabbits fed rabbit chow containing 860 ppm nimodipine. Aging control rabbits are dramatically impaired in the acquisition of this task compared to young controls. Aging rabbits receiving nimodipine reached a behavioral criterion of 4 conditioned responses in any block of 5 trials significantly faster than aging controls. Young controls reached this criterion faster than the aging controls. There were no significant group effects on either the amplitude or the latency of the conditioned response. This study extends earlier reports that IV nimodipine enhances the associative learning abilities of aging rabbits and examined the route of administration most likely to be used clinically in aging humans.

Aging↗
PubMedDate not supplied

Trace eyeblink conditioning in rabbits demonstrates heterogeneity of learning ability both between and within age groups.

Rabbits 2 to 41 months of age were conditioned in the 500 ms trace eyeblink paradigm to cross-sectionally define the age of onset and the severity of age-associated impairments in acquisition of this relatively difficult hippocampally dependent task. Using a strict behavioral criterion of 80% conditioned responses (CRs), age-associated learning impairments were significant by 24 months of age. Among rabbits that successfully reached this criterion, impairments in acquisition plateaued at 30 months of age. However, the proportion of severely impaired rabbits (that failed to reach the 80% criterion) continued to increase age dependently. Using an easier criterion of 8 out of 10 CRs, behavioral impairments were not detected until 30 months of age, and cases of severe impairment (failure to reach criterion) were rare. Additional controls demonstrated that the deficits observed were not attributable to nonassociative changes that might have artifactually skewed the data. Even severely impaired 36-month-old rabbits were able to reach a criterion of 80% CRs when switched from a trace to a delay conditioning task that is not hippocampally dependent. The results are discussed in terms of operationally defining and predicting behavioral effects of aging, hypothetical neural mechanisms, and efficient experimental design.

Age Factors↗
PubMedDate not supplied

Nimodipine ameliorates aging-related changes in open-field behaviors of the rabbit.

The open-field behavior of old rabbits (32-50 months) was compared to that of young-controls (3 months). Old rabbits engaged in less grooming and rearing behaviors and were more active than young controls. The old rabbits demonstrated a pattern of ambulation which did not indicate a preference for any particular area of the open-field. In contrast, young rabbits exhibited a very stereotypic pattern of exploration in the open-field, engaging in relatively low levels of ambulation confined to the area near the sides of the open-field. Old rabbits fed a diet which included 860 ppm nimodipine showed behaviors in the open-field which closely approximated those of the young-controls. Nimodipine-treated rabbits made fewer crossings and more rears and grooms than the old controls. These results indicate that very specific aging-related changes occur in the open-field behaviors of rabbits, and that nimodipine effectively reverses these aging-associated changes. These data are consistent with previous studies that have shown improvements in open-field behaviors by old rats receiving nimodipine.

Aging↗