Endogenous regulators of long-term potentiation and depression in rat olfactory cortex slices

A perfusate collected from tetanized donor slices of rat olfactory cortex was separated by ultrafiltration into fractions containing substances with molecular weights of less than and greater than 50 kDal. Each fraction was separately tested on recipient slices. The fraction with substances of greater than 50 kDal elicited long-term depression of focal potentials in recipient slices. The fraction with substances of less than 50 kDal mainly induced activation. The chemical nature of the factors released during tetanization was studied by treating the high-molecular-weight fraction with immobilized trypsin; after proteolytic treatment this fraction produced a qualitatively different response in recipient slices, suggesting that the active factors were polypeptides. These data indicate that donor slice cells release a set of neurohumoral substances, probably polypeptides, during tetanization, which are involved in the modulation of synaptic plasticity. Laboratory for the Regulation of Brain Neuron Function (M. O. Samoilov, Director); Laboratory of Functional Neurochemistry (N. A. Emel'yanov, Director), I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg. Translated from Fiziologicheskii Zhurnal im I. M. Sechenova, Vol. 81, No. 8, pp. 39–44, August, 1995.     

Peroxidative oxidation of lipids in slices of olfactory cortex of the rat brain during long-term potentiation

The content of the products of the peroxidative oxidation of lipids (POL) in slices of olfactory cortex of the rat brain during long-term potentiation was investigated. The phasic character of the changes in the level of POL as a function of the duration of potentiation was demonstrated. The initial stages of potentiation (5 min) is characterized by an increase in POL; the stationary phase (15 min) is accompanied by inhibition of free-radical oxidation of lipids; the concluding phase of long-term potentiation (30 min) leads to the normalization of POL. The dynamics of the change in POL reflect the adaptive character of the development of potentiation in the slices. Laboratory of Functional Neurochemistry, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 80, No. 8, pp. 43–47, August, 1994.     

45Ca exchange in rat cortex slices in conditions of long-term potentiation

Existing data on the role of Ca²⁺ ions in the development of long-term potentiation were used as a basis for studying changes in different Ca²⁺ compartments in cells in living rat olfactory cortex slices during potentiation. The kinetics of⁴⁵Ca²⁺ exchange were studied at 5, 15, and 30 min of potentiation. During the induction phase (1–5 min) of long-term potentiation, the fraction of tightly-bound intracellular Ca²⁺ decreased. There were no changes in the content of Ca²⁺ ions in other fractions at this stage. During maintenance of potentiation, which lasted 15–25 min, Ca²⁺ levels in the extracellular and intracellular compartments did not differ from controls. At 30 min, during extinction of long-term potentiation, there was a significant redistribution of Ca²⁺ in cells: the levels of free and loosely-bound Ca increased, as did extracellular Ca²⁺. Laboratory of Functional Neurochemistry, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, St. Petersburg 199034, Russia. Translated from Rossiiki Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 7, pp. 45–49, July, 1997.     

Effect of hydrocortisone on synaptic transmission in surviving rat olfactory cortex slices

A study has been made of the effect of bath-applied hydrocortisone (10^–4 M) on excitatory transmission of the lateral olfactory tract (LOT), a superficial pyramidal cell synapse of the rat olfactory cortex slice. Populations EPSP and IPSP were depressed for 6–12 min and were then increased (60 min) by hydrocortisone. Recovery of evoked potentials was prolonged (40–60 min) when slices were washed with normal incubation medium. Habituation of synaptic potential during LOT repeated stimulation deteriorated as a result of hydrocortisone application in perfusion solution. The data obtained were considered to represent functions of adaption of the nervous system to a stressor.Translated from Problemy Éndokrinologii, Vol. 34, No. 6, pp. 52–56, November–December, 1988     

Effect of hypobaric hypoxia on the development of long-term posttetanic potentiation in slices of rat olfactory cortex: Correction with hypoxic preconditioning

We studied the effect of in vivo hypobaric hypoxia on the development (after 3 h) of in vitro long-term posttetanic potentiation in Wistar rats. Severe hypoxia suppressed induction of posttetanic potentiation in slices of the olfactory cortex. Preconditioning exposure (moderate hypobaric hypoxia) prevented inhibition of posttetanic potentiation induced by severe hypoxia. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 11, pp. 487–489, November, 2006     

Afferent and association fiber differences in short-term potentiation in piriform (olfactory) cortex of the rat

1. The effects of low-frequency stimulus trains on synaptically evoked responses in piriform cortex pyramidal cells were studied by the use of intracellular recording techniques in an in vitro slice preparation. Afferent and association fiber systems were differentially stimulated with electrodes placed in layer 1a or layer 1b, respectively. To quantify synapse modifiability, the heights of postsynaptic potentials (PSPs) elicited by paired-pulse stimulation (100-ms interval) were averaged over a 50-s period before and after a set of 10 stimulus trains (10 pulses each, 20 Hz, 5-s interpulse interval). 2. Afferent and association fibers showed consistent differences in their response to stimulation during the period lasting from approximately 10 to 200 s after presentation of trains. During this time period, the responses to stimulation of association fibers in layer 1b displayed a short-term potentiation, which over the 10 posttrain trials, produced an average increase in PSP height of 23.2 +/- 3.7% (mean +/- SE). On the other hand, responses to layer 1a stimulation showed an average depression of 10.9 +/- 3.6%. Layer 1b potentiation decayed with time constant roughly estimated at 79 s. Layer 1b potentiation appeared even at very low stimulus voltages and after local association fiber input had been cut, suggesting that it was largely a monosynaptic effect. 3. In the period immediately after train presentations, responses evoked by both layers showed a short-term augmentation with a time constant around 3 s. In layer 1a, this augmentation was superimposed on a depression with slow recovery. At longer times after train presentation (greater than 5 min), 2 cells out of 46 showed changes (increases) in synaptic efficacy in response to layer 1b stimulation. 4. In the current experiments both layers 1a and 1b showed statistically significant facilitation before the presentation of stimulus trains. However, layer 1b facilitation decreased from 22.7 +/- 3.5% to a statistically insignificant 3.9 +/- 3.3% after the presentation of trains, whereas layer 1a facilitation remained at a statistically significant level of 23.1 +/- 5.7%. 5. These experiments show that pyramidal cell responses to stimulation of the afferent and association fiber systems are affected differently by the previous presentation of trains of stimuli. This suggests that mechanisms of synaptic modification may differ between the afferent and intrinsic association synaptic projections onto single pyramidal cells in olfactory cortex.(ABSTRACT TRUNCATED AT 400 WORDS)     

Benzodiazepines block long-term potentiation in slices of hippocampus and piriform cortex.

The effects of two benzodiazepines, diazepam and triazolam, on long-term potentiation were tested in slices of hippocampus and piriform cortex. The drugs had little influence on baseline synaptic responses but both were very effective in blocking LTP elicited by theta pattern stimulation. The effects were fully reversible upon washout. Diazepam reduced the increase in burst responses that occurs during theta stimulation and thus appears to interfere with the initial triggering events for long-term potentiation. This may reflect the enhancing action of the drug on GABA-mediated inhibitory potentials. Triazolam did not detectably change the burst responses elicited by theta pattern stimulation. Experiments with slices of piriform cortex indicated that triazolam also failed to disrupt the development of long-term potentiation but instead caused the potentiation to decay back to baseline in 15-30 min. Triazolam thus seems to act on the mechanisms that stabilize long-term potentiation. These results provide a possible explanation for the amnestic effects of benzodiazepines in humans and animals and support the hypothesis that long-term potentiation contributes to memory encoding.     

Posttetanic potentiation of primary response and late negative wave in the somatosensory region of the cortex of the cat

The experiments were carried out on cats under nembutal anesthesia. Stimulation of the ventroposterolateral nucleus of the thalamus or the white matter by a single stimulus elicited a primary response in the middle layers of the somatosensory cortex, and after it, a late negative wave, the duration of which reaches 40–70 msec. This potential does not have dipole reflection on the surface of the cortex and is apparently generated primarily by stellate cells. As a result of the tetanization of the ventroposterolateral nucleus or the white matter, a sharp increase in the amplitude of the late negative wave is observed, i. e., its postteanic potentiation, while the primary response changes to a significantly lesser degree. Posttetanic potentiation is observed for 2–2.5 h. Posttetanic potentiation of the late negative wave is probably governed by processes occurring at the level of the middle layers of the cerbral cortex.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 75, No. 10, pp. 1328–1334, October, 1989.     

Two-deoxyglucose-induced long-term potentiation in slices of rat dentrate gyrus

In keeping with previous observations in the CA1 and the somatosensory neocortex of the brain of rat, 20-min applications of 2-deoxy-D-glucose (2DG; 10 mM, replacing glucose) induced a long-term potentiation (LTP)-like enhancement of field excitatory synaptic potentials (fEPSPs) in the dentate region of hippocampal slices. The effects of 2DG were not identical at synapses of medial and lateral perforant paths (MPP and LPP). At MPP synapses, there was no post-2DG early depression of fEPSPs and the potentiation reached +78.6 +/- 5.7 % (+/- standard error of the mean) 40 min after the return to glucose. In the presence of 50 microM D-amino-phosphono valerate (APV; an N-methyl-D-aspartate [NMDA] receptor antagonist), a marked post-2DG depression appeared and the subsequent LTP was reduced to +34.7 +/- 2.8 % (for both 2DG- and APV-treatment P<0.001 by ANOVA-2W). At LPP synapses, even under control conditions, there was a sharp post-2DG depression followed by LTP (+62.2 +/- 5.7 %) and APV had little effect on either the post-2DG depression or LTP, reducing the latter by only 24 % [the 2DG treatment was very significant (P<0.001) but not the APV treatment]. Thus, 2DG evokes both NMDAR-dependent and -independent components of LTP in the perforant pathways. In view of these findings, the consumption of 2DG could have significant effects on synaptic plasticity and cognitive function.     

Pyroglutamyl-Asparagine amide normalizes long-term potentiation in rat hippocampal slices

Preapplication of peptide piracetam analogue pyroglutamyl-asparagine amide to rat hippocampal slices facilitates long-term potentiation of focal responses in the CA1 field after weak tetanization of the synaptic input (30 pulses, 100 Hz). This treatment normalized the development of long-term potentiation after standard tetanization (100 pulses, 100 Hz) impaired by ethanol. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 176–179, August, 2004 This work was supported by the Russian Foundation for Basic Research (grant No. 01-04-48304).     

Sleep deprivation impairs long-term potentiation in rat hippocampal slices

To determine if 12-h sleep deprivation disrupts neural plasticity, we compared long-term potentiation (LTP) in five sleep-deprived and five control rats. Thirty minutes after tetanus population spike amplitude increased 101 +/- 15% in 16 slices from sleep deprived rats and 139 +/- 14% in 14 slices from control rats. This significant (P < 0.05) reduction of LTP, the first demonstration that the sleep deprivation protocol impairs plasticity in adult rats, may be due to several factors. Reduced LTP may indicate that sleep provides a period of recuperation for cellular processes underlying neural plasticity. Alternatively, the stress of sleep deprivation, as indicated by elevated blood corticosterone levels, or other non-sleep-specific factors of deprivation may contribute to the LTP reduction.     

Heterogeneous spatial patterns of long-term potentiation in rat hippocampal slices

Although LTP (long-term potentiation) of synaptic transmission has received much attention as a model for learning and memory, its function within a neural circuit context remains poorly understood. To monitor LTP over an extensive circuit, we imaged responses in hippocampal slices using a voltage-sensitive dye. Following theta-burst stimulation, evoked optical signals showed an increase that lasted 40 min or more. Weak stimuli only potentiated the local area around the stimulating electrode, but stronger stimuli induced LTP over a wide area with a complex and non-uniform spatial pattern. The expression of LTP showed distinct peaks and valleys that depended on which axons were activated. Interestingly, the spatial distribution of LTP bore no relation to the spatial distribution of single-shock responses, but closely resembled the distribution of postsynaptic spikes evoked by theta bursts. Thus, postsynaptic spikes during induction constitute a critical determinant for the expression of LTP in intact circuits.     

High-frequency magnetic stimulation induces long-term potentiation in rat hippocampal slices

Recent reports indicate that the exposure of brain tissues to transcranial magnetic stimulation induces persistent changes in neuronal activity and influences hippocampal synaptic plasticity. However, the modulation of synaptic efficiency by magnetic stimulation in vitro is still unclear. In the present study, we investigated whether high-frequency magnetic stimulation (HFMS) can induce long-term potentiation (LTP) in rat hippocampal slices in vitro. During baseline recording and after HFMS, field excitatory postsynaptic potentials (fEPSPs) were recorded within the CA1 stratum radiatum in response to electrical stimulation of the Schaffer collateral inputs. For LTP induction, HFMS was delivered through a circular coil positioned closely above the slices using two different paradigms (A: 10 trains of 20 pulses at 100 Hz with 1 s intervals, 5 repetitions with 10 s intervals; B: 3 trains of 100 pulses at 100 Hz with 20 s intervals). The intensity of the magnetic stimulus was adjusted to 60–75 A/μs. After application of HFMS, electrically evoked CA1 fEPSPs were enhanced showing significant levels of LTP by both paradigms (A: 142 ± 9% of baseline, n = 6; B: 129 ± 7%, n = 8). Furthermore, HFMS-induced LTP induced by paradigm A was prevented by the presence of the selective N-methyl-d-aspartate receptor (NMDAR) blocker D-AP5 (50 μM) in the bath solution (95 ± 6% of the baseline, n = 6; p < 0.01 compared to control condition without D-AP5). Further, the lack of changes in paired-pulse ratio and the afferent fiber volleys exclude presynaptic involvement in HFMS-induced LTP. In summary, we have demonstrated that HFMS can induce NMDAR-dependent LTP in the CA1 region in vitro.     

Preconditioning hypobaric hypoxia prevents anoxia-induced inhibition of generation of focal potentials in slices of olfactory cortex from rat brain

We studied the effect of in vivo exposure to hypobaric hypoxia of different depth on the resistance of neurons in brain slices to 10-min anoxia in vitro. Severe hypoxia simulating ascent to 11,000 m above sea level potentiated the adverse effect of 10-min anoxia and caused profound suppression of synaptic transmission. Moderate preconditioning hypoxia simulating ascent to 5000 m above sea level produced a long-lasting protective effect on synaptic activity.     

Possible presynaptic inhibition in rat olfactory cortex.

1. Field potentials were evoked from rat olfactory cortex slices in vitro at room temperature by lateral olfactory tract stimulation. At very slow stimulation rates (less than 0-1 Hz) a delayed negative wave (late N-wave) was found to follow the first negative wave (N-wave). This late N-wave started 30 msec after the stimulus and lasted for 50-150 msec. 2. Low Ca2+/high Mg2+ medium abolished the late N-wave more rapidly than the N-wave, suggesting a possible multisynaptic origin. 3. The GABA antagonist bicuculline (10(-6) M) abolished the late N-wave without affecting the N-wave. 4. During the late N-wave, both the tract action potential and the N-wave to a second stimulus were reduced. This was attributed, at least in part, to collision with antidromic action potentials which could be detected during the late N-wave. 5. These findings are discussed in terms of a possible presynaptic depolarizing action of a GABA-like transmitter giving rise to presynaptic inhibition and the late N-wave.     

Number of correlates of membrane metabolism and long-term potentiation in rat brain slices

Long-term potentiation was elicited in living slices of rat olfactory cortex by stimulation of the lateral olfactory tract. A group of interdependent parameters of membrane metabolism was studied, i.e., the kinetics of⁴⁵Ca metabolism, lipid peroxidation, and antioxidant defense; cytochemical measurements were made of Na⁺, K⁺-ATPase activity in neurons and glial cells; the functional (GTPase) activity of G-proteins was also studied. All parameters were compared with the bioelectrical activity of slices at three time points after tetanization, i.e., 3–5, 15, and 30 min. In most cases, regular phasic changes in metabolic parameters occurred, and their functional significance is discussed. Laboratory of Functional Neurochemistry (N. A. Emel'yanov, Director), I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg. Translated from Fiziologicheskii Zhurnal im. I. M. Sechenova, Vol. 81, No. 8, pp. 29–33, August, 1995.