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L T Thompson

Publications and source records attributed to L T Thompson.

At least 19 recordsLinked to original sources
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↗
PubMed1999

Metrifonate increases neuronal excitability in CA1 pyramidal neurons from both young and aging rabbit hippocampus.

The effects of metrifonate, a second generation cholinesterase inhibitor, were examined on CA1 pyramidal neurons from hippocampal slices of young and aging rabbits using current-clamp, intracellular recording techniques. Bath perfusion of metrifonate (10-200 microM) dose-dependently decreased both postburst afterhyperpolarization (AHP) and spike frequency adaptation (accommodation) in neurons from young and aging rabbits (AHP: p < 0.002, young; p < 0.050, aging; accommodation: p < 0.024, young; p < 0.001, aging). These reductions were mediated by muscarinic cholinergic transmission, because they were blocked by addition of atropine (1 microM) to the perfusate. The effects of chronic metrifonate treatment (12 mg/kg for 3 weeks) on CA1 neurons of aging rabbits were also examined ex vivo. Neurons from aging rabbits chronically treated with metrifonate had significantly reduced spike frequency accommodation, compared with vehicle-treated rabbits. Chronic metrifonate treatment did not result in a desensitization to metrifonate ex vivo, because bath perfusion of metrifonate (50 microM) significantly decreased the AHP and accommodation in neurons from both chronically metrifonate- and vehicle-treated aging rabbits. We propose that the facilitating effect of chronic metrifonate treatment on acquisition of hippocampus-dependent tasks such as trace eyeblink conditioning by aging subjects may be caused by this increased excitability of CA1 pyramidal neurons.

Action Potentials↗
PubMed1997

Metrifonate treatment enhances acquisition of eyeblink conditioning in aging rabbits.

The cholinergic system is known to show deterioration during aging and Alzheimer's disease. In response, a therapeutic approach to Alzheimer's disease has been to attempt to compensate for the decrease in central cholinergic function by potentiating the activity of the remaining intact cholinergic cells with cholinesterase inhibitors. In this study treatment with the long-lasting cholinesterase inhibitor metrifonate enhanced acquisition of eyeblink conditioning in aging rabbits without producing interfering side effects. The effects of metrifonate on central and peripheral cholinesterase activity were evaluated, as was the involvement of plasma atropine esterase activity on the central and peripheral response to metrifonate. Results demonstrate that metrifonate can produce predictable, dose-dependent ChE inhibition. Associative learning in the aging rabbit was improved by metrifonate-induced steady state ChE inhibition within a range of 30-80%. Metrifonate was behaviorally effective in the absence of the severe side effects which typically plague cholinesterase inhibitors, suggesting that metrifonate is a possible treatment for the cognitive deficits resulting from normal aging and Alzheimer's disease.

Aging↗
PubMed1997

Age- and dose-dependent facilitation of associative eyeblink conditioning by D-cycloserine in rabbits.

Normal aging selectively impairs some forms of learning. For example, aging rabbits require more than twice as many trials to acquire 500-ms trace eyeblink conditioning than do young rabbits. N-methyl-D-aspartate (NMDA) receptor antagonists also impair trace conditioning. The effects of daily D-cycloserine (DCS; a partial agonist of the NMDA receptor-glycine site) treatment were tested on trace conditioning of young or aging rabbits using a conservative quantitative approach. DCS dose dependently improved acquisition, maximally reducing trials to criterion by approximately 50%. Dose-response curves were right-shifted by aging (twice the dose was required to achieve the same enhancement compared with controls). DCS did not affect nonassociative performance but sharpened the conditioned stimulus tone intensity discrimination. DCS thus can functionally modulate NMDA receptors in normal aging, enhance associative learning at all ages, and reduce or reverse age-dependent learning deficits.

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↗
PubMed1997

N-methyl-D-aspartate receptors in associative eyeblink conditioning: both MK-801 and phencyclidine produce task- and dose-dependent impairments.

The effects of N-methyl-D-aspartate receptor blockade on two major variants of rabbit eyeblink conditioning were evaluated using a selective noncompetitive antagonist, [5R, 10S]-[+]-5-methyl-10, 11-dihydro-5H-dibenzo[a, d] cyclo-hepten-5,10-imine hydrogen maleate; dizocilpine (MK-801) or phencyclidine (PCP), a drug of abuse. Either MK-801 or PCP (given daily) impaired rabbits' ability to associate tone conditioned stimuli with airpuff unconditioned stimuli, with the severity of impairment exhibiting clear dose and task dependencies. Trace-conditioned rabbits given > or = 80 micrograms/kg of MK-801 or > or = 1.0 mg/kg of PCP failed to reach a criterion of 80% conditioned responses during training, with significant impairments seen at intermediate doses. Delay-conditioned rabbits, although dose-dependently slowed, successfully acquired the task, even when given doses of MK-801 or PCP that completely blocked acquisition in trace conditioning. Additionally, even low doses of MK-801 (10 micrograms/kg) or of PCP (0.1 mg/kg) severely altered conditioned response timing in trace but not in delay conditioning, resembling effects observed after hippocampal lesions. Doses of MK-801 or PCP that impaired acquisition also severely impaired extinction of both trace- and delay-conditioned eyeblink responses. However, neither MK-801 nor PCP altered retention or timing of previously learned responses. Higher doses of MK-801 (> or = 200 micrograms/kg) or of PCP (> or = 2.0 mg/kg) dose-dependently impaired unconditioned response performance, although lower doses of MK-801 (< or = 160 micrograms/kg) or of PCP (< or = 1.0 mg/kg) had no effects on unconditioned responses or on non-associative pseudoconditioned responses. The deficits observed indicate that although not necessary for retention, N-methyl-D-aspartate receptor activation may facilitate acquisition of delay-conditioning. N-methyl-D-aspartate receptor activation appears to be necessary for acquisition of trace conditioning, and for extinction in either paradigm.

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

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↗
PubMed1994

A system for quantitative analysis of associative learning. Part 2. Real-time software for MS-DOS microcomputers.

Microcomputer software was designed and used to control the timing and delivery of sensory stimuli and to acquire and analyze behavioral data during classical conditioning experiments. The software package runs under DOS 4.x through 6.x (earlier versions run under DOS 3.x) on PC AT-compatible microcomputers coupled with appropriate interface hardware (see Thompson et al., 1994). The software controls timed delivery of up to 8 conditional stimuli. It can collect behavioral data from 2 subjects simultaneously performing the same task (e.g., eyeblink responses) or from a single subject performing 2 different tasks (e.g., both eyeblink and conditional discrimination tasks), permitting its use in a number of experimental paradigms. Digital timing signals are adjustable for different stimulus output systems. Behavior is continuously monitored onscreen, ensuring consistent measurement across trials. Real-time performance measures of the presence or absence of conditioned responses allow coordination with external events (e.g., serum sampling, drug delivery, or single-unit recording). Quantitative measures are generated both for each trial and for complete sessions. Records are stored to disk and can be printed or merged for statistical analyses. Data can be archived on standard media, and internal software utilities translate files for export to PC and Macintosh programs. This system and the hardware described in the preceding paper combine ease of use with extremely replicable behavioral measurements across trials, sessions subjects, cohorts, and studies.

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

Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine.

Persistent neuronal plasticity, including that observed at some hippocampal synapses, requires N-methyl-D-aspartate (NMDA)-mediated transmission. NMDA receptor activation may be necessary for hippocampus-dependent learning as antagonists block acquisition in many such tasks. The behavioural effects of NMDA agonists are less well defined. We have shown that a monoclonal antibody (B6B21) displaced [3H]-glycine that was bound specifically to the NMDA receptor, and enhanced the opening of its integral cation channel in a glycine-like fashion, effects that were competitively antagonized by 7-chlorokynurenic acid. B6B21 also enhanced long-term potentiation in hippocampal slices. We report here that intraventricular infusions of B6B21 significantly enhances acquisition rates in hippocampus-dependent trace eye blink conditioning in rabbits, halving the number of trials required to reach a criterion of 80% conditioned responses. Peripheral injections of D-cycloserine, a partial agonist of the glycine site on the NMDA receptor which crosses the blood-brain barrier, also doubles rabbits' learning rates. Pseudoconditioning control experiments indicated a lack of nonspecific behavioural sensitization effects. Our data suggest that enhanced activation of the glycine coagonist site on the NMDA receptor/channel complex facilitates one form of associative learning and may be used in other learning tasks.

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

Nimodipine enhances spontaneous activity of hippocampal pyramidal neurons in aging rabbits at a dose that facilitates associative learning.

The functional activity of hippocampal neurons is strongly correlated with behavioral performance in a vertebrate model learning system, rabbit eyeblink conditioning. Using this system, we have previously shown that (a) complete removal of the hippocampus blocks acquisition of the conditioned response; (b) a calcium-dependent postsynaptic afterhyperpolarization is reduced in pyramidal cells recorded intracellularly in hippocampal slices taken from conditioned rabbits; and (c) nimodipine, a 1,4-dihydropyridine calcium-channel antagonist, facilitates acquisition of the conditioned response in aging rabbits. Although calcium-channel antagonists directly block neuronal calcium currents in vitro, they also alter cerebral blood flow in vivo. Thus, the effects of nimodipine on hippocampal neuronal activity in awake animals were examined, with controls for cerebrovascular changes. A total of 457 pyramidal cells and 160 theta cells were studied. During infusion of nimodipine, pyramidal cell firing activity was enhanced and theta interneuron activity was suppressed at all doses tested in aging animals. This effect was rapidly reversed when infusion of the drug ceased. The greatest enhancement of neuronal firing was seen at the most behaviorally effective dose of nimodipine. The enhancement of pyramidal cell firing was age-dependent, with greater increases in firing activity seen in aging than in young animals, but with a similar dose-dependent pattern of effects in the two age groups. Two other calcium-channel antagonists, nifedipine and flunarizine, did not significantly alter spontaneous firing rates of hippocampal neurons. A calcium-channel agonist, BAY-K-8644, produced less easily interpretable results. BAY-K-8644 enhanced interneuron activity at one dose, but enhanced pyramidal cell activity at a dose one log unit higher. The calcium-channel agonist's enhancement of pyramidal cell activity at the highest dose was sustained up to 1 h after drug infusion. Nimodipine's enhancement of the activity of hippocampal pyramidal cells is consistent with the hypothesis that these neurons, which play a necessary role in some forms of learning, may mediate the calcium-channel antagonist's behavioral effects.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Long-term stability of the place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats.

Over 90% of all spontaneously active hippocampal pyramidal cells in freely moving rats signal the animal's spatial position by reliably changing their firing rate each time the animal enters a given place within an environment. This place-field activity exhibits plasticity when specific environmental variables are manipulated. Indeed, the hippocampus is perhaps best known as a system that serves as a model of neuronal plasticity. Although place-field activity has previously been examined only over relatively short experimental sessions, this behavioral correlate of hippocampal functional activity has been assumed to exhibit stability rather than plasticity in the absence of environmental changes. The present study shows that hippocampal neurons have stable place-field correlates that persist over very long periods of time. Single-unit activity was chronically recorded from the dorsal hippocampus of rats foraging repeatedly in a stable spatial environment. The location of the place fields of all units were stable over all time periods tested, for intervals up to 153 days in duration. The consistency of the information conveyed by this single-unit activity in a fixed spatial environment indicates that stability of neuronal activity may be as important as plasticity in the integrated processing of information that occurs in the hippocampus and throughout the nervous system.

Action Potentials↗
PubMed1989

Place cells and silent cells in the hippocampus of freely-behaving rats.

In the present study, nearly two-thirds of all hippocampal pyramidal units isolated under barbiturate anesthesia, which maximizes these cell's activity, were behaviorally silent. These "silent cells" showed no spontaneous firing activity in the awake, freely-behaving rat. Both reanesthetization and antidromic stimulation, however, activated these silent cells. More than 92% of the remaining spontaneously active hippocampal pyramidal cells recorded from freely-behaving rats were place cells; i.e., they exhibited spatially specific changes in firing activity in at least one environment. The firing rates of these place cells varied depending on the animal's location in this environment. Interestingly many of these place cells displayed low or no spontaneous activity and no spatial specificity in other, dissimilar environments; i.e., their lack of firing in some spatial environments mirrored the behavioral silence of the more numerous silent cells reported here. In complex information processing, such as the processing of spatial information by the hippocampus demonstrated here, neural silence may be as important a signal as neural activity.

Animals↗