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Biomedical subjects

J D Bronzino

Publications and source records attributed to J D Bronzino.

At least 19 recordsLinked to original sources

Frequency-dependent changes in the paired-pulse index in the hippocampus of the freely moving adult male rat.

The paired-pulse index (PPI) has been widely used as a measure of modulation of cellular excitability in the hippocampal trisynaptic circuit. This paper presents a quantification of the changes in this measure of neuronal modulation as a result of the application of pulse trains having six different train frequencies (0.1, 1, 5, 8, 15, and 30 Hz) to one of the major efferent pathways to the dentate gyrus, the medial perforant path (MPP). Our findings indicate that the modulation of the first leg of the hippocampal trisynaptic circuit is dependent on the frequency of the "burst train" applied to the perforant pathway. This methodological finding is of importance to all investigators studying hippocampal plasticity via LTP or LTD approaches. The different synaptic mechanisms implicated in being responsible for the changes in the PPI are also discussed.

Afferent Pathways↗

Increased extracellular release of hippocampal NE is associated with tetanization of the medial perforant pathway in the freely moving adult male rat.

The induction of long-term potentiation (LTP) within the dentate gyrus of the hippocampal formation is modulated by many afferent influences from a number of subcortical structures known to be intimately involved in hippocampal-dependent learning and memory. It has been demonstrated in slice and anesthetized preparations that norepinephrine (NE) is one of these major neuromodulators involved in the induction of LTP. However, the majority of these studies have not been conducted in the freely moving animal. Recently, we developed surgical procedures and instrumentation techniques to simultaneously record electrophysiological and neurochemical data from the hippocampal formation. The present study uses these techniques to examine the underlying neurochemical changes in the hippocampus associated with the induction of hippocampal dentate LTP in the freely moving adult rat. These findings establish baseline levels of NE that can be used to evaluate the impact of various tetanization paradigms as well as the effect of a variety of insults on hippocampal plasticity.

Animals↗

The effect of interburst intervals on measures of hippocampal LTP in the freely moving adult male rat.

An important factor in the induction and maintenance of long-term potentiation (LTP) is the tetanization paradigm. This paper presents the changes associated with the induction and maintenance of hippocampal LTP in the freely moving adult male rat, subjected to three different tetanization paradigms. These results indicate that specific LTP measures including (1) synaptic activation, as measured by the slope of the dentate granule cell population excitatory postsynaptic potential, and (2) cellular response, as measured by the dentate population spike amplitude, evoked by single-pulse stimulation of the medial perforant pathway are dependent on the interburst interval of the bursting paradigm commonly used in LTP studies.

Animals↗

Modulation of paired-pulse responses in the dentate gyrus: effects of normal maturation and vigilance state.

This study examined the effect of normal development and vigilance state on the modulation of dentate granule cell activity in the freely moving rat at 15, 30, and 90 days of age across three vigilance states: quiet waking, slow-wave sleep, and rapid eye movement sleep. Using paired-pulse stimulation, the paired-pulse index (PPI) was obtained for the dentate evoked field potentials elicited by the stimulation of the medial perforant path. Although significant differences in PPI values were observed during development, no significant vigilance state related changes were obtained. Preweaning infant rats, i.e., 15-day old, exhibited significantly less early (interpulse intervals, IPI= 20-50 ms) and late (IPI = 300-1,000 ms) inhibition, and less facilitation (IPI = 50-150 ms) when compared to the 90-day old adult rats during all three vigilance states. PPI values obtained from the 30-day old group fell intermediate between the 15- and 90-day old animals. These changes in PPI values provide a quantitative measure of changes in the modulation of dentate granule cell excitability during normal maturation. They can now can be used to evaluate the impact of various insults, such as prenatal protein malnutrition or neonatal stress, on hippocampal development.

Animals↗

Modulation of paired-pulse responses in the dentate gyrus: effects of prenatal protein malnutrition.

Since our major hypothesis is that prenatal protein malnutrition significantly affects hippocampal neuroplasticity, this study examined the effects of prenatal protein malnutrition on the modulation of dentate granule cell excitability in freely moving rats at 15, 30 and 90 days of age across the vigilance states of quiet waking (QW), slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Using paired-pulse stimulation, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability elicited by stimulation of the medial perforant path, was obtained for each vigilance state at each stage of development. Four specific measures of granule cell excitability were computed, namely, PPI using both population spike amplitude (PSA) and EPSP slope measures, absolute values of PSA(1) and EPSP(1) slope. PPI values obtained at 15, 30 and 90 days of age, however, were altered during normal ontogenetic development, but not by vigilance state. At 15 days of age, the malnourished group exhibits greater early inhibition of the PPI using the PSA measure at IPIs between 20 and 30 ms regardless of vigilance state, while at 30 days of age, the malnourished group exhibits greater facilitation at IPIs between 50 and 70 ms during QW and SWS, but not during REM sleep. In the control adult (PND90) and juvenile (PND30) animal, PSA(1) values are significantly higher during SWS than in QW or REM sleep. However, for the younger malnourished animals (PND15 and PND30), PSA(1) values were found to be significantly greater during REM sleep rather than SWS. Therefore, as the animal matures, there appears to be a shift in vigilance state dependent synaptic transmission through the hippocampal trisynaptic circuit from REM sleep to SWS in both control and malnourished animals, with the change occurring later in malnourished animals when compared to control ones. Furthermore, our findings suggests that prenatal protein malnutrition significantly alters modulation of dentate granule cell excitability (i.e., PPI values using the PSA measure) during the earlier stages of development but not in adulthood.

Aging↗

The effects of median raphé electrical stimulation on serotonin release in the dorsal hippocampal formation of prenatally protein malnourished rats.

Our previous work had shown an enhanced inhibition in the hippocampal formation of prenatally protein malnourished rats. We have also found a diminishment in 5-hydroxytryptamine (5-HT) fibers in the hippocampal formation of malnourished rats as well as increased levels of 5-HT in the brain. The purpose of the present study was to determine 5-HT release in the dorsal hippocampal formation following electrical stimulation of the median raphé nucleus (MRN) in unanesthetized prenatally malnourished rats. Stimulation of this nucleus at 20 Hz in malnourished rats resulted in a significantly diminished release of 5-HT compared to well-nourished rats. The latter group showed a lesser, though still significant, decrease in 5-HT release following raphé stimulation. Basal release of 5-HT prior to stimulation was significantly higher in malnourished rats as compared to well-nourished controls. This may be the result of a decreased density of 5-HT neurons leading to a diminished control of release. Stimulation of the MRN in behaving malnourished animals may markedly affect the recurrent negative feedback collaterals onto somatodendritic 5-HT(1A) and 5-HT(1D) autoreceptors thus enhancing the inhibitory effects of stimulation of the median raphé on 5-HT release. Studies are underway to examine the sensitivity of both the somatodendritic and terminal 5-HT autoreceptors in malnourished animals, in order to understand possible mechanisms for our findings.

Analysis of Variance↗

Dentate granule cell modulation in freely moving rats: vigilance state effects.

Dentate granule cell population responses to paired-pulse stimulation applied to the perforant pathway across a range of interpulse intervals (IPIs) were examined during different vigilance states-quiet waking (QW), slow-wave sleep (SWS), and rapid-eye movement (REM) sleep-in freely moving rats at 15, 30 and 90 days of age. Using these evoked field potentials, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability, was computed and shown to be altered as a function of age. Animals, 15 days old, showed significantly lower levels of early inhibition (20-40 ms IPIs), i.e., greater PPI values, during all three vigilance states when compared to both the 30- and 90-day old animals. Adult, i.e, 90-day old animals, on the other hand, showed significantly greater levels of late inhibition (300-1000 ms IPIs), i.e., lower PPI values, than the younger animals (15- and 30-day old) during QW and SWS. These results indicate that as the dentate field of the hippocampal formation matures there are significant alterations in the modulation of dentate granule cell activity.

Animals↗

Neonatal stress alters LTP in freely moving male and female adult rats.

We previously reported that neonatal isolation stress significantly changes measures of hippocampal long-term potentiation (LTP) in male and female juvenile rats, i.e., at 30 days of age. The changes in dentate granule population measures, i.e., excitatory postsynaptic potential (EPSP) and population spike amplitude (PSA), evoked by tetanization of the medial perforant pathway, indicated that juvenile rats exposed to neonatal isolation exhibit different enhancement profiles with respect to both the magnitude and duration of LTP in a sex-specific manner. Isolated males showed a significantly greater enhancement of LTP, while female "isolates" showed significantly longer LTP duration when compared to all other groups. The present study was designed to determine whether the effects of the neonatal isolation stress paradigm endures into adulthood. Rats isolated from their mothers for 1 h per day during postnatal days 2-9 were surgically prepared at 70-90 days of age, with stimulating and recording electrodes placed in the medial perforant pathway and the hippocampal dentate gyrus, respectively. Prior to tetanization, no significant effect of sex or treatment was obtained for baseline measures of EPSP slope or PSA. In order to rule out baseline differences in hippocampal cell excitability in female adult rats, we measured the response of dentate granule cells for one estrus cycle and found no pretetanization enhancement in the evoked response in either controls or previously stressed rats. Following tetanization, there was a significant treatment and sex effect. During the induction of LTP, PSA values were significantly enhanced in both isolated males and females and had significantly longer LTP duration when compared to the unhandled control group. Additionally, we observed that females took longer to reach baseline levels than males. Taken together, these results indicate that repeated infant isolation stress enhances LTP induction and duration in both males and females. These results indicate that infant stress alters hippocampal neuroplasticity in such a way that its effect endures into adulthood.

Age Factors↗

Hippocampal neurochemical and electrophysiological measures from freely moving rats.

This paper describes surgical and recording procedures that have been developed which permit the simultaneous monitoring of levels of select neurochemicals (via microdialysis) and measures of dentate-evoked field potentials within the hippocampal formation of freely moving adult rats. To test and evaluate these procedures, they were employed to examine changes in hippocampal neurochemistry and neuronal excitability associated with the establishment and maintenance of hippocampal long-term potentiation (LTP). Measures of hippocampal norepinephrine (NE) and glutamate levels along with measures of the dentate granule cell population spike amplitude (PSA) were obtained before, during, and after tetanization of the medial perforant path using two separate tetanization paradigms. Results obtained using these new procedures in several animals indicated that changes in NE and glutamate levels were strongly correlated with increases in the dentate granule cell PSA measure obtained following tetanization. The results indicate that this newly developed procedure can be effectively used to directly examine the relationship between neurochemical and neurophysiological changes associated with hippocampal neuroplasticity.

Animals↗

Serotonin neuronal release from dorsal hippocampus following electrical stimulation of the dorsal and median raphé nuclei in conscious rats.

We have studied 5-hydroxytryptamine (5-HT) release in the hippocampal formation following electrical stimulation of the dorsal and median raphé nuclei in the behaving rat. The primary finding in this study is a decrease in neuronal release of serotonin in the dorsal hippocampal formation following electrical stimulation of either the dorsal or median raphé nucleus in conscious rats. At no time did electrical stimulation of either raphé nucleus result in behavioral, including vigilance state, changes. The amount of 5-HT released was found to be frequency dependent with higher frequencies (20 Hz) producing larger decreases in release of 5-HT. However, the pattern of release differs between the two raphé nuclei. Extracellular levels of 5-HT decrease during stimulation of the dorsal raphé, whereas levels decrease only following cessation of stimulation of the median raphé nucleus. This may relate to the patterns of innervation of the dorsal hippocampal formation by these two midbrain raphé nuclei and also may reflect an inhibition of median raphé cell firing during stimulation of the dorsal raphé. Electrical stimulation of the dorsal raphé in anesthetized animals resulted in an enhanced release of 5-HT. The suppression of 5-HT release in the dorsal hippocampal formation in behaving animals was long-lasting (over 2 h), suggesting that the control mechanisms that regulate 5-HT release operate over a long time-course. This difference in release between non-anesthetized and anesthetized animals may relate to anesthesia blocking long- and/or short-loop serotonin recurrent axonal collaterals negatively feeding back onto 5-HT1A and 5-HT1D somatodendritic autoreceptors on raphé neurons. Further, the anesthetized animal has diminished monoaminergic "gating" influences on the hippocampal formation, whereas the behaving animal is more complex with behavioral (vigilance) states associated with different patterns of gating of information flow through the hippocampal formation.

Animals↗

Effects of prenatal protein malnutrition on hippocampal long-term potentiation in freely moving rats.

It has been demonstrated that prenatal protein malnutrition significantly affects hippocampal plasticity, as measured by long-term potentiation, throughout development. This paper focuses on the hippocampal dentate granule cell population response to two separate paradigms of tetanization of the medial perforant pathway in prenatally protein-malnourished and normally nourished adult male rats. The 100-pulse paradigm consisted of the application of ten 25-ms-duration bursts of 400 Hz stimulation with an interburst interval of 10 s. The 1000-pulse paradigm consisted of the application of five 500-ms bursts of 400 Hz stimulation with an interburst interval of 5 s. No between-group differences were obtained for input/output response measures prior to tetanization. No between-group, nor between-paradigm, differences were obtained in the degree of population EPSP slope enhancement. However, in response to both paradigms, prenatally malnourished animals showed significantly less enhancement of the population spike amplitude (PSA) measure than normally nourished animals. Normally nourished animals showed a significantly greater level of PSA enhancement in response to the 100-pulse paradigm than the 1000-pulse paradigm. Prenatally malnourished animals showed no significant differences in the degree of PSA enhancement between the two paradigms. Results indicate that short duration bursts (< or = 25 ms) are more effective in inducing maximal PSA enhancement in normally nourished rats than longer duration stimulus bursts. The apparent inability of prenatally malnourished rats to transfer enhanced cellular activation (population EPSP slope enhancement) into enhanced cellular discharge (PSA enhancement) suggests that a preferential enhancement of GABAergic inhibitory modulation of granule cell excitability may result from the prenatal dietary insult. Such potentiation of inhibitory activity would significantly lower the probability of granule cell population discharge, resulting in the significantly lower level of PSA enhancement obtained from these animals.

Animals↗

Studies of dentate granule cell modulation: paired-pulse responses in freely moving rats at three ages.

Dentate granule cell population responses to paired-pulse stimulations applied to the perforant pathway across a range of interpulse intervals (IPI) were examined in freely moving rats at 15, 30, and 90 days of age. The profile of the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability, was shown to change significantly as a function of age.

Animals↗

Diet-induced alterations in the ontogeny of long-term potentiation.

The ability of prenatally malnourished rats to establish and maintain long-term potentiation (LTP) of the perforant path/dentate granule cell synapse was examined in freely moving rats at 15, 30, and 90 days of age. Measures of the population EPSP slope and population spike amplitude (PSA) were calculated from dentate field potential recordings obtained prior to and at various times following tetanization of the perforant pathway. Significant enhancement of both population EPSP slope and PSA measures was obtained from all animals of both malnourished and well-nourished diet groups at 15 days of age. However, the magnitude of enhancement obtained from 15-day-old prenatally malnourished animals was significantly less than that of age-matched, well-nourished controls. At 30 days of age, PSA measures obtained from approximately 50% of prenatally malnourished 30-day-old rats showed no significant effect of tetanization, while measures obtained from the remaining 50% of these animals did not differ significantly from controls. EPSP slope measures for this age group followed much the same pattern, i.e., malnourished animals showing no significant enhancement of PSA measures exhibited only slight increases in EPSP slope beginning 1 h after tetanization and returned to baseline by 18 h post-tetanization. EPSP slope measures obtained from PSA-enhanced malnourished animals did not differ significantly from controls. At 90 days of age, PSA measures obtained from 50% of malnourished animals declined from pretetanization levels immediately following tetanization. Three hours after tetanization, however, this measure had increased to a level which did not differ significantly from that of the control group. PSA measures obtained from the remaining 50% of 90-day-old malnourished animals showed initial and sustained enhancement which did not differ significantly from those obtained from well-nourished age-matched controls. These results indicate that gestational protein malnutrition significantly affects the magnitude of tetanization-induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals) and significantly alters the time-course and magnitude of potentiation in approximately half of prenatally malnourished animals tested at 30 and 90 days of age. Given the primarily postnatal development of the dentate granule cells, these results may reflect malnutrition-induced delays in the neurogenesis and functional development of granule cells previously reported by our group. Most striking is the fact that significant impairments in LTP establishment were obtained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation commencing at birth is an intervention strategy incapable of ameliorating the effects of the gestational insult.

Action Potentials↗

Neonatal isolation alters LTP in freely moving juvenile rats: sex differences.

We have previously reported that neonatal isolation significantly enhanced the magnitude of hippocampal long-term potentiation (LTP) recorded from freely moving male rats tested at 30 days of age. The present study extends this work to examine the effects of neonatal isolation on hippocampal LTP in male and female juvenile rats. Changes in dentate granule cell population measures, i.e., EPSP slope and population spike amplitude (PSA), evoked by tetanization of the medial perforant pathway were used to assess the effects of neonatal isolation on LTP over a period of 96 hrs. Prior to tetanization, significant sex differences were obtained for input/output (I/O) response measures of EPSP slope and PSA, with males showing consistently higher values than females. No significant effect of treatment was obtained within either sex for baseline measures. Following tetanization significant sex differences were also obtained for both measures, with males showing significantly greater enhancement than females. Comparisons made at 1 hr post-tetanization (establishment of LTP) indicated that isolated males showed significantly greater enhancement than any other group. On the other hand, treatment differences were not obtained from females. At 96 hrs (maintenance of LTP), however, both neonatally isolated males and females showed significantly greater enhancement than either non-isolated siblings or unhandled controls. These results indicate that males and females exhibit different enhancement profiles with respect to both the magnitude and duration of LTP, and that neonatal isolation alters these profiles in a sex-specific manner.

Animals↗

Effects of an every other day rapid kindling procedure in prenatally protein malnourished rats.

Prenatally protein (6/25) rats have been reported to require significantly more stimulations to attain a stage 5 seizure than well-nourished controls (25/25) when using either a traditional or rapid every day, kindling procedure. In the present study, a rapid kindling procedure was utilized where both prenatally malnourished and control rats received every other day perforant path kindling (50 Hz, 10 s train) 12 times a day at 5-min intervals. Using this procedure, stage 5 seizures and a fully state were attained in both nutritional groups at approximately the same rate. It is postulated that it is the every other day component of the present procedure which overcomes seizure-induced inhibition in the 6/25 subjects, thereby allowing them to attain stage 5 seizures at the same rate as controls.

Animal Nutritional Physiological Phenomena↗

Neonatal isolation enhances hippocampal dentate response to tetanization in freely moving juvenile male rats.

The impact of early neonatal isolation on measures of hippocampal neuronal plasticity was examined in freely moving male rats at 30 days of age. Beginning on Postnatal (PN) Day 2, one-half of pups from each experimental litter were individually isolated from the nest, dam, and siblings for a period of 1 h per day over PN Days 2-9, while their siblings remained in the nest. In addition, randomly selected litters served as unhandled controls. On PN Day 26 all pups were weaned and chronically implanted for recording of evoked field potentials and induction of hippocampal longterm potentiation. At 30 days of age, pups from the three treatment groups (isolated, nonisolated siblings, and unhandled controls) were tested for their ability to establish and maintain long-term potentiation across the perforant path/hippocampal dentate granule cell synapse. Changes in population EPSP slope and population spike amplitude (PSA) recorded following tetanization were used to assess the effects of neonatal isolation of hippocampal response measures. No significant between-group differences were obtained for input/output response curves constructed prior to tetanization. All three groups showed immediate and significant enhancement of the PSA measure at 15 min posttetanization. The level of PSA enhancement obtained from previously isolated pups was significantly greater than that obtained from both the nonisolated sibling and unhandled control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantitative analysis of long-term potentiation in the hippocampal dentate gyrus of the freely-moving 15-day-old rat.

The magnitude and duration of long-term potentiation (LTP) of perforant path/dentate granule cell synapses was examined in freely moving rats beginning at 15 days of age. Measures of dentate granule cell population EPSP slope and population spike amplitude (PSA) obtained before and after tetanization were used to evaluate the level of LTP. Tetanization resulted in significant enhancement of both the population EPSP slope (approximately +75%) and PSA (approximately +40%) measures. This enhancement was maintained without significant change for 18 h, after which both measures began a steady and continuous rise. Daily input/output response measures from age-matched nontetanized animals were used to factor out enhancement related to normal development. Under this schema, tetanization-induced enhancement of both EPSP slope and PSA measures decayed slowly, beginning 18-24 h after tetanization, returning to baseline 5 days after tetanization. Enhancement obtained from 90-day-old animals decayed to baseline 24 h after tetanization. The longer duration of LTP obtained from preweanlings is discussed with regard to the development of inhibitory systems modulating granule cell excitability.

Animals↗