Associative synaptic plasticity in hippocampus and visual cortex: cellular mechanisms and functional implications

Synchronous pre- and postsynaptic neuronal activity results in long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus and the neocortex. Induction of this form of potentiation requires calcium influx mediated by NMDA receptors. Experimental evidence is reviewed for induction of long-term depression (LTD) of synaptic transmission in the hippocampus in vitro and neocortical neurons in vivo, when the discharge of the postsynaptic neuron is temporally decorrelated from the presynaptic stimulation. Homosynaptic LTD induced by low frequency tetani in the hippocampus in vitro requires NMDA receptor activation and a moderate calcium influx. The role of postsynaptic calcium as a key parameter in the encoding of temporal contiguity of neural activity and its possible implications in the formation of engrams during specific learning tasks are discussed.     

Intrahippocampal GMP administration improves inhibitory avoidance performance through GABAergic and glutamatergic mechanisms in rats

Guanidino compounds play specific physiological and pathological roles in the central nervous system. We investigated the effect of an intrahippocampal infusion of GMP (a guanidino compound) administered immediately post-training on the inhibitory avoidance learning paradigm in rats. Bilateral intrahippocampal micro-injection of GMP (0-30 nmol) caused a dose-dependent increase in test step-down latencies which was completely reversed by intrahippocampal co-administration of muscimol or baclofen (GABA agonists) or preadministration (15 min pre-training, i.p.) of MK-801 (an NMDA antagonist). These results provide evidence for a participation of GABA and NMDA receptors in the GMP-induced increase in the test step-down latencies.     

Influence of ethanol on the pentylenetetrazol-induced kindling in rats

The effects of ethanol on the development of pentylenetetrazol (PTZ)-kindling as well as on fully PTZ-kindled convulsions in rats were investigated. Ethanol (0.5, 1.0 and 1.5 g/kg i.p.) administered 15 min prior to each PTZ-injection (35 mg/kg i.p.; 3 times/week) significantly inhibited the progressive seizure development compared to saline-treated controls. For the higher doses of ethanol the kindling process was restricted to seizure stages of 1 or 2. Tolerance to this antiepileptogenic action did not occur even after 20 PTZ-stimulations. In a second series of experiments, 0.5 g/kg ethanol administered 10h before each PTZ-injection facilitated the rate of kindling development after 7 to 10 PTZ-injections, while the higher doses of ethanol did not modulate or even slightly reduced the seizure development. In a third test, intermittent administration of a high dose of ethanol (2 g/kg p.o.; twice daily for 6 days) before the kindling procedure (0.5 g/kg i.p. ethanol 10h prior to each PTZ-injection), significantly intensified the kindling development. In addition, studies with fully PTZ-kindled rats demonstrated that ethanol (0.1 to 1.5 g/kg i.p.), given 15 min prior or 2 min after PTZ, reduced the seizure severity in a dose-dependent manner. In conclusion, the present findings provide evidence for pronounced antiepileptogenic and anticonvulsant effects of ethanol after acute application, whereas repeated administration of high doses with longer withdrawal periods leads to proconvulsant actions, possible mediated via neuroadaptive changes in NMDA and/or GABA(A) receptor-related mechanisms.     

Effect of pentylenetetrazol treatment on cholecystokinin mRNA and peptide levels in rat hippocampus and cortex

After treatment with pentylenetetrazol (PTZ), cholecystokinin (CCK) mRNA and CCK-like immunoreactivity (CCK-LI) levels were determined in rat hippocampus and cortex at different time points. In the temporal cortex treatment with 60 mg/kg PTZ, i.p., induced increases of CCK mRNA and CCK-LI levels at 2 days after the injection. In the hippocampus, a similar increase of CCK mRNA level was observed on the second day. By contrast, in the frontal cortex, CCK-LI level was increased at 10 days after the treatment with PTZ. These data show that PTZ increases both CCK mRNA and CCK-LI levels in these rat brain regions at different time.     

Long-term potentiation of synaptic transmission in the avian hippocampus

The avian hippocampus plays a pivotal role in memory required for spatial navigation and food storing. Here we have examined synaptic transmission and plasticity within the hippocampal formation of the domestic chicken using an in vitro slice preparation. With the use of sharp microelectrodes we have shown that excitatory synaptic inputs in this structure are glutamatergic and activate both NMDA- and AMPA-type receptors on the postsynaptic membrane. In response to tetanic stimulation, the EPSP displayed a robust long-term potentiation (LTP) lasting >1 hr. This LTP was unaffected by blockade of NMDA receptors or chelation of postsynaptic calcium. Application of forskolin increased the EPSP and reduced paired-pulse facilitation (PPF), indicating an increase in release probability. In contrast, LTP was not associated with a change in the PPF ratio. Induction of LTP did not occlude the effects of forskolin. Thus, in contrast to NMDA receptor-independent LTP in the mammalian brain, LTP in the chicken hippocampus is not attributable to a change in the probability of transmitter release and does not require activation of adenylyl cyclase. These findings indicate that a novel form of synaptic plasticity might underlie learning in the avian hippocampus.     

Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus

The neurotrophins are signaling factors important for the differentiation and survival of distinct neuronal populations during development. To test whether the neurotrophins also function in the mature nervous system, the effects of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophic factor 3 (NT-3) on the strength of synaptic transmission in hippocampal slices were determined. Application of BDNF or NT-3 produced a dramatic and sustained (2 to 3 hours) enhancement of synaptic strength at the Schaffer collateral-CA1 synapses; NGF was without significant effect. The enhancement was blocked by K252a, an inhibitor of receptor tyrosine kinases. BDNF and NT-3 decreased paired-pulse facilitation, which is consistent with a possible presynaptic modification. Long-term potentiation could still be elicited in slices previously potentiated by exposure to the neurotrophic factors, which implies that these two forms of plasticity may use at least partially independent cellular mechanisms.     

The effect of kavinton on the erythron system and the blood gas composition in rats

The effects of cavinton on serum erythropoietin levels, erythrocytic 2,3-DFG concentrations, acid-balance and lactic acid concentrations were studied in normal rats for 24 hours. The findings suggest that there might be two possible mechanisms of cavinton's action at the level of erythron: 1) impact on the determinants of hemoglobin functional properties; 2) creation of a potential for enhancing the production of erythropoietin.     

The effect of GABAergic system activity on hyperthermia-induced seizures in rats

Developing rats were given GABA antagonists and agonist before electrical seizure discharges were induced by heating the brain of a rat with infra-red rays. The thresholds for the GABA antagonist groups were significantly lower than that for the control, and the threshold for the GABA agonist group was significantly higher than that for the control. These results support the hypothesis that reduced GABAergic system activity underlies febrile seizures.     

Bidirectional long-term modification of synaptic effectiveness in the adult and immature hippocampus

Previously we showed that delivering 900 pulses to the Schaffer collateral-CA1 pathway at 1-3 Hz causes a lasting depression of synaptic effectiveness that is input specific and dependent on NMDA receptor activation (Dudek and Bear, 1992a). Here we describe experiments aimed at further characterizing this homosynaptic long-term depression (LTD) and comparing it with long-term potentiation (LTP). To address the question of whether depressed synapses can still be potentiated and vice versa, LTP was saturated with repeated high-frequency tetani, and then LTD was induced with low-frequency stimulation (LFS). A second strong tetanus then restored the potentiation, indicating that the same synapses whose transmission had been depressed by LFS were capable of subsequently supporting potentiation. In a complementary experiment, LTD was induced first and then a strong high-frequency tetanus was delivered. We found that the resulting LTP achieved the same absolute magnitude as that observed in control slices that had received the high-frequency stimulation alone. Next, the postnatal development of LTD was investigated in slices prepared from rats at 6-35 d of age. The consequences of LFS were far more pronounced in slices from young rats. LTD following 900 pulses at 1 Hz measured -45 +/- 4% in CA1 of rats less than 2 weeks old as compared with -20 +/- 4 in animals at 5 weeks postnatal. It was also found that LTD precedes the developmental onset of LTP in CA1. Finally, we addressed the question of whether LTD could be saturated by repeated episodes of LFS in slices prepared from 3-week-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of neuronal growth on synaptic integration

The way in which the dimensions of neurons change during postembryonic development has important effects on their electrotonic structures. Theoretically, only one mode of growth can conserve the electrotonic structures of growing neurons without employing changes in membrane electrical properties. If the dendritic diameters of a neuron increase as the square of the increase in dendritic lengths, then the neuron's electrotonic structure is conserved. We call this special mode of allometric growth "isoelectrotonic growth." In this study we compared the developmental changes in morphology of two identified invertebrate neurons with theoretical growth curves. We found that a cricket neuron, MGI, grows isoelectrotonically and thereby preserves its electrotonic properties. In contrast, the crayfish neuron, LG, grows in nearly isometric manner resulting in an increase in its electrotonic length.     

Reinforcing properties of ethanol in neonatal rats: Involvement of the opioid system.

Toward understanding why infant rats ingest high levels of ethanol without initiation procedures, the authors tested effects of mu and kappa receptor antagonists on ethanol reinforcement in neonatal rats. After an intracisternal injection of CTOP (mu antagonist), nor-Binaltorphimine (kappa antagonist), or saline, newborn (3-hr-old) rats were given conditioning pairings of an odor with intraorally infused ethanol or a surrogate nipple with ethanol administered intraperitoneally (to minimize ethanol's gustatory attributes). In each case, these opioid antagonists reduced or eliminated ethanol's reinforcement effect. The same effects occurred with saccharin as the reinforcer in olfactory conditioning. The results imply that activation of mu and kappa receptors, apparently acting jointly, is necessary for reinforcement or that antagonists of this activity impair basic conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanisms underlying the enhancement of excitatory synaptic transmission in basolateral amygdala neurons of the kindling rat

To elucidate the mechanism underlying epileptiform discharges in kindled rats, synaptic responses in kindled basolateral amygdala neurons in vitro were compared with those from control rats by using intracellular and whole cell patch-clamp recordings. In kindled neurons, electrical stimulation of the stria terminalis induced epileptiform discharges. The resting potential, apparent input resistance, current-voltage relationship of the membrane, and the threshold, amplitude, and duration of action potentials in kindled neurons were not different from those in control neurons. The electrical stimulation of stria terminalis elicited excitatory postsynaptic potentials (EPSPs) and DL-2-amino-5-phosphonopentanoic acid (AP5)-sensitive and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic currents (EPSCs). The amplitude of evoked EPSPs and of evoked AP5-sensitive and CNQX-sensitive EPSCs were enhanced markedly, whereas fast and slow inhibitory postsynaptic potentials (IPSPs) induced by electrical stimulation of lateral amygdaloid nucleus were not significantly different. The rise time and the decay time constant of the evoked CNQX-sensitive EPSCs were shortened, whereas the rise time of the evoked AP5-sensitive EPSCs was shortened, but the decay time constants were not significantly different. In both tetrodotoxin (TTX)-containing medium and low Ca2+ and TTX-containing medium, the frequency and amplitude of spontaneous EPSCs were increased in kindled neurons. These increases are presumably due to nearly synchronous multiquantal events resulted from the increased probability of Glu release at the nerve terminals. The rise time of evoked CNQX- and AP5-sensitive EPSCs and the decay time constant of evoked CNQX-sensitive EPSCs were shortened, suggesting that excitatory synapses at the proximal dendrite and/or the soma in kindled neurons may contribute more effectively to generate evoked EPSCs than those at distal dendrites. In conclusion, the increases in the amplitudes of spontaneous and evoked EPSCs and in the frequency of spontaneous EPSCs may contribute to the epileptiform discharges in kindled neurons.     

The effect of opioid antagonists in local regulation of testicular response to acute stress in adult rats

The present study examined the effects of naloxone (N) and naltrexone-methobromide (NMB; an opioid receptor antagonist that does not cross the blood-brain barrier) on testicular steroidogenesis during acute immobilization stress (IMO; 2 h) in adult rats. Unstressed rats as well as IMO rats were treated by unilateral intratesticular injection of N (20 micrograms/testis), NMB (36 micrograms/testis), or vehicle at the beginning of and at 1 h of the IMO period. In IMO rats serum T levels were significantly reduced, while serum luteinizing hormone levels were not affected. N and NMB normalized serum T levels in IMO rats and had no effects in controls. In IMO rats the activities of 3 beta-hydroxysteroid dehydrogenase (HSD) and P450(17 alpha, lyase) were significantly reduced, while the activity of 17 beta-HSD was not affected. N and NMB antagonized the inhibitory effect of IMO on 3 beta-HSD and P450(17 alpha, lyase) but did not alter enzyme activity in freely moving rats. Acute IMO decreased basal and human chorionic gonadotropin-stimulated androgen production by hemitestis preparation, but N (10(-4) M) added directly to the incubation medium blocked the decrease and had no effect on testes from freely moving control rats. These results support the conclusion that endogenous opioid peptides are potentially important paracrine regulators of testicular steroidogenesis under stress conditions.     

The role of the endogenous opioid system in regulation of the nonspecific resistance of the myocardium to reperfusion injury in rats

Under conditions of postischemic reperfusion, significance of endogenous opioid receptors' agonists for regulation of the myocardial contractility becomes enhanced. The sigma-receptor blocking contributes to a decrease in postischemic contracture and preservation of the cardiac cell membrane integrity. In sigma-receptor blockade, reoxygenation contracture does not appear. Preliminary mu-receptor blocking leads to an almost complete restitution of the heart contractility and decreases sarcolemma damage during postischemic period.     

Corticotrophin-releasing factor produces a long-lasting enhancement of synaptic efficacy in the hippocampus

We have previously demonstrated that intra-hippocampal injection of corticotrophin-releasing factor improved memory retention of an inhibitory avoidance learning in rats; while the electrophysiological effects corticotrophin-releasing factor produces on hippocampal neurons are largely uncharacterized. In the present study, we found that corticotrophin-releasing factor injected into the dentate gyrus of hippocampus produced a dose-dependent and long-lasting enhancement in synaptic efficacy of these neurons, as measured by an increase in the amplitude and slope of population excitatory postsynaptic potentials, as well as the amplitude of population spike. The onset of corticotrophin-releasing factor-induced potentiation was slow. It was observed approximately 40-60 min after corticotrophin-releasing factor administration and lasted for more than 5 h. This effect of corticotrophin-releasing factor was blocked by pretreatment with the cyclase-adenosine-3,5-monophosphate (cAMP) inhibitor Rp-adenosine-3,5-cyclic monophosphothiolate triethylamine (Rp-cAMPS) and partially blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Further, pretreatment with corticotrophin-releasing factor receptor antagonist dose-dependently diminished tetanization-induced long-term potentiation, and corticotrophin-releasing factor and tetanic stimuli had an additive effect on hippocampal neuron excitation. Moreover, direct injection of corticotrophin-releasing factor increased cAMP level in the dentate gyrus. These results together suggest that corticotrophin-releasing factor-induced potentiation simulates the late phase of tetanization-induced long-term potentiation and cAMP seems to be the messenger mediating this effect. Moreover, corticotrophin-releasing factor-induced potentiation and long-term potentiation may share some similar mechanisms, and corticotrophin-releasing factor is probably involved in the neural circuits underlying long-term potentiation. Thus, corticotrophin-releasing factor may play an important role in modulating synaptic plasticity in the hippocampus.     

Assessing the roles of glutamatergic and cholinergic synaptic drive in the control of fictive swimming frequency in young Xenopus tadpoles

Nine athletes (seven football offensive linemen, one defensive lineman, and one lacrosse player) were found at arthroscopy to have posterior labral detachment from the glenoid. In our series, this lesion is specific to contact athletes who engage their opponents with arms in front of the body. All patients had pain with bench pressing and while participating in their sport, diminishing their ability to play effectively. Conservative measures were ineffective in relieving their symptoms. Examination under anesthesia revealed symmetric glenohumeral translation bilaterally, without evidence of posterior instability. Treatment consisted of glenoid rim abradement and posterior labral repair with a bioabsorbable tack. All patients returned to complete at least one full season of contact sports and weightlifting without pain (minimum follow-up, > or = 2 years). Although many injuries leading to subluxation of the glenohumeral joint occur when an unanticipated force is applied, contact athletes ready their shoulder muscles in anticipation of impact with opponents. This leads to a compressive force at the glenohumeral joint. We hypothesize that, in combination with a posteriorly directed force at impact, the resultant vector is a shearing force to the posterior labrum and articular surface. Repeated exposure leads to posterior labral detachment without capsular injury. Posterior labral reattachment provides consistently good results, allowing the athlete to return to competition.