Effects of different concentrations of calcitonin gene-related peptide on long-term depression of hippocampus in mice / 生理学报

The purpose of this study was to explore the effects of calcitonin gene-related peptide (CGRP) on the long-term depression (LTD) of hippocampus in mice. Sixty C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP (50, 100, and 200 nmol/L) groups, CGRP + CGRP group and CGRP + APV group (10 mice for each group). The effects of exogenous application of different concentrations of CGRP on synaptic plasticity and LTD in hippocampus of mice were detected by in vitro recording of local field potential. The results showed that higher doses (100 and 200 nmol/L) of CGRP significantly enhanced the induction of LTD in the hippocampus. Moreover, CGRP increased the magnitude of N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents. The above-mentioned effects of CGRP were blocked by either CGRP selective antagonist CGRP or NMDA receptor antagonist APV. These results suggest that CGRP can dose-dependently enhance the induction of LTD in hippocampus of mice, and the underlying mechanism involves the mediation of NMDA receptor function.

Involvement of aquaporin-4 in synaptic plasticity, learning and memory / 生理学报

Aquaporin-4 (AQP-4) is the predominant water channel in the central nervous system (CNS) and primarily expressed in astrocytes. Astrocytes have been generally believed to play important roles in regulating synaptic plasticity and information processing. However, the role of AQP-4 in regulating synaptic plasticity, learning and memory, cognitive function is only beginning to be investigated. It is well known that synaptic plasticity is the prime candidate for mediating of learning and memory. Long term potentiation (LTP) and long term depression (LTD) are two forms of synaptic plasticity, and they share some but not all the properties and mechanisms. Hippocampus is a part of limbic system that is particularly important in regulation of learning and memory. This article is to review some research progresses of the function of AQP-4 in synaptic plasticity, learning and memory, and propose the possible role of AQP-4 as a new target in the treatment of cognitive dysfunction.

Post-activation depression of the lower extremities in stroke patients with spasticity and spastic equinovarus deformity / Depressão pós-ativação das extremidades inferiores de pacientes com acidente vascular cerebral que apresentam espasticidade e deformidade equinovarus por espasticidade

This study aimed to investigate changes of post-activation depression in two groups of patients with or without spastic equinovarus deformity (SED). Paired and independent t-tests were used to compare post-activation depression within and between the groups, respectively. There was a significant positive correlation between diminished post-activation depression and spasticity severity. The soleus and tibialis anterior (TA) post-activation depression values were significantly decreased on the affected sides of patients with SED compared to those without. In patients without SED, the soleus post-activation depression was significantly decreased on the affected side; however, TA post-activation depression was higher on the affected side. Both the soleus and TA become active, but the onset time may be different. The imbalanced muscle tone between the soleus and TA in the early stage after stroke may be related to equinus deformity.

O principal objetivo deste estudo é a investigação da depressão pós-ativação em pacientes com deformidade equinovarus espástica (DEE). Os pacientes foram divididos em dois grupos. Student-t testes pareados e independentes foram utilizados para comparar a depressão pós-ativação intra- e inter-grupos, respectivamente. Houve uma correlação positiva significativa entre a diminuição da depressão pós-ativação e a gravidade da espasticidade. A depressão pós-ativação dos músculos sóleo e tibial anterior (TA) estavam significativamente diminuídas no lado afetado dos pacientes com SEE em relação aos membros sem SEE. Em pacientes sem SEE, a depressão pós-ativação do músculo sóleo encontrava-se significativamente diminuída do lado afetado. No entanto, a depressão pós-ativação do músculo TA era maior no lado afetado que no lado não afetado. Tanto o sóleo quanto o TA serão ativados, mas o tempo para isso pode ser diferente. O desequilíbrio entre o tônus dos músculos sóleo e TA nos estágios iniciais pode estar relacionado à deformidade equina.

Roles of protein synthesis inhibitors in long-term potentiation and depotentiation in hippocampal CA1 region of adult rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the roles of protein synthesis inhibitors in long-term potentiation(LTP) and depotentiation(DP) in hippocampal CA1 region of adult rats.</p><p><b>METHODS</b>Standard extracellular recording technique was used to record field EPSP(fEPSP) evoked by Schaffer collateral stimulation from the CA1 subfield of adult rat hippocampal slices. Paired-pulse low-frequency stimulation(PP-LFS) or high-intensity paired-pulse low-frequency stimulation(HI-PP-LFS) was delivered to induce depotentiation 2 h after LTP induction induced by six theta-burst stimulations. Protein synthesis inhibitors were applied before and after LTP induction to study their roles in LTP and DP in hippocampal CA1 region of adult rats.</p><p><b>RESULTS</b>When HI-PP-LFS was applied at 2 h after LTP induction, the depotentiation was induced. The mean fEPSP slopes reduced from 346.2%±26.3% to 207.1%±21.6%. This depotentiation was named as partial LTP depotentiation and maintained at least for 30 min. The percentage of depotentiation was 59.81%. Application of protein synthesis inhibitors, anisomycin and cycloheximide prior to tetanus resulted in smaller LTP compared to control group, and almost complete depotentiation was induced by HI-PP-LFS. With application of protein synthesis inhibitors anisomycin and cycloheximide 90 min after LTP induction, HI-PP-LFS still induced partial LTP depotentiation. However, there was no significant difference in the percentage of depotentiation between this group and control group.</p><p><b>CONCLUSION</b>HI-PP-LFS partially reverses late phase LTP. When protein synthesis inhibitors are applied prior to tetanus, LTP amplitude is markedly reduced, and HI-PP-LFS completely reverses late-phase LTP. Application of protein synthesis inhibitors after LTP induction does not significantly affect either the amplitude or depotentiation of LTP.</p>

Molecular Mechanisms Involved in Depotentiation and Their Relevance to Schizophrenia / 전남의대학술지

Long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission are forms of synaptic plasticity that have been studied extensively and are thought to contribute to learning and memory. The reversal of LTP, known as depotentiation (DP) has received far less attention however, and its role in behavior is also far from clear. Recently, deficits in depotentiation have been observed in models of schizophrenia, suggesting that a greater understanding of this form of synaptic plasticity may help reveal the physiological alterations that underlie symptoms experienced by patients. This review therefore seeks to summarize the current state of knowledge on DP, and then put the deficits in DP in models of disease into this context.

Molecular Mechanisms Involved in Depotentiation and Their Relevance to Schizophrenia / 전남의대학술지

Long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission are forms of synaptic plasticity that have been studied extensively and are thought to contribute to learning and memory. The reversal of LTP, known as depotentiation (DP) has received far less attention however, and its role in behavior is also far from clear. Recently, deficits in depotentiation have been observed in models of schizophrenia, suggesting that a greater understanding of this form of synaptic plasticity may help reveal the physiological alterations that underlie symptoms experienced by patients. This review therefore seeks to summarize the current state of knowledge on DP, and then put the deficits in DP in models of disease into this context.

Chronic effects of oligomeric Aβ(1-42) on hippocampal synaptic plasticity in vivo / 生理学报

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is widely considered as one of the major mechanisms underlying learning and memory. This study explored hippocampal synaptic plasticity and spatial memory formation of an Alzheimer's disease (AD) rat model established by intrahippocampal injection of oligomeric Aβ(1-42). Twenty four Sprague-Dawley rats at 2.5 months of age were randomly divided into AD and control groups, and were bilaterally injected with 5 μg oligomeric Aβ(1-42) or normal saline into dentate gyrus (DG) of hippocampus. Morris water maze test was used to observe the capability of learning and memory of two groups, 30 d after injection. To investigate the variations of paired-pulse facilitation (PPF) and range of synaptic plasticity, field potentials were recorded in the DG of the dorsal hippocampus by stimulating the perforant path (PP). The results showed that oligomeric Aβ(1-42) obviously impaired spatial memory formation in rats (P < 0.05). Furthermore, oligomeric Aβ(1-42) reduced the PPF ratio (P < 0.05) and hippocampal LTP formation (P < 0.05), while facilitated the hippocampal LTD formation (P < 0.05). These data suggest that chronic Aβ aggregation impairs synaptic plasticity of hippocampal PP-DG pathway, which may be involved in the spatial memory deficit in AD rats.

Long term depression of the recurrent inhibition of monosynaptic spinal reflexes after sciatic nerve crush in adult rats / 生理学报

Sciatic nerve injury is a common disease of peripheral nerve in clinic. After nerve injury, there are many dysfunctions in motoneurons and muscles following regeneration. Previous studies mostly investigated the aspects related to the injured nerve, and the effect on the recurrent inhibition (RI) pathway of spine following regeneration was not fully understood. Following reinnervation after temporary sciatic nerve crush, the functional alteration of RI was studied. In adult rats, RI between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSRs) elicited from the cut dorsal roots and recorded from either the LG-S or MG nerves by antidromic stimulation of the synergist muscle nerve. The following results were obtained. (1) The RI of MSRs in rats was almost lost (<5 weeks) after sciatic nerve crush. Although the RI partially recovered following reinnervation (6 weeks), it remained permanently depressed (up to 14 weeks). (2) Sciatic nerve crush on one side did not affect the contralateral RI. (3) Sciatic nerve crush did not induce any motoneuron loss revealed by immunohistochemistry. Peripheral nerve temporary disconnection causes long term alterations in RI pathway which make up motoneuron's function enhance for the alteration of muscle power and suggests that peripheral nerve injury induces long term plastic changes in the spinal motoneuron circuitry.

Long-term potentiation and long-term depression: a clinical perspective

Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

Antidepressant activity of fosinopril, ramipril and losartan, but not of lisinopril in depressive paradigms of albino rats and mice.

Fosinopril, ramipril and losartan significantly decreased the duration (sec) of immobility in forced swim test and were comparable to amitriptyline. The duration of immobility were significantly decreased in fosinopril, ramipril and losartan in the tail suspension test and were comparable to amitriptyline. Only losartan significantly increased the rearing number of entries, time spent (sec) in open arm and in light area in comparison to control animals. Fosinopril and ramipril and not lisinopril showed significant antidepressant activity while losartan showed a significant antidepressant and anxiolytic activity. Present findings suggest that these drugs could be better antihypertensives in hypertensive patients with comorbidity like depression or anxiety.

Different glutamate receptor mechanisms in long-term depression induced by different stimulus patterns in the CA1 area of adult rat hippocampus / 生理学报

Previous reports suggested that a novel stimulus pattern of multi-train stimulus at low-frequency (2-Hz or 5-Hz) could induce stable long-term depression (LTD) in the CA1 area of adult rat hippocampus. In the present study, in order to determine the mechanism in LTD induced by the two novel tetanus patterns, changes in the population spikes (PS) in the hippocampal CA1 area of adult rats following the multi-train stimulus in the presence of AP5 [antagonist of N-methyl-D-aspartate receptors (NMDARs)] or MCPG [antagonist of type I/II metabotropic glutamate receptors (mGluRs)] were recorded. The results showed that both AP5 and MCPG inhibited the LTD induced by 2-Hz multi-train stimulus. The mean amplitude of population spikes (PSA) normalized to the baseline was (96.0±3.5)% after applying AP5 (n=10) and (95.7±4.1)% after applying MCPG (n=8), respectively, measured at 20 min post-tetanus. While 5-Hz multi-train tetanus failed to induce LTD in the presence of MCPG. The mean PSA was (73.6±4.4)% (n=10) and (98.2±8.9)% (n=8) in the presence of AP5 and MCPG, respectively, measured at 35 min post-tetanus. So it is suggested that LTD induced by 2-Hz multi-train tetanus involves co-activation of NMDARs and mGluRs, while LTD induced by 5-Hz multi-train tetanus is only related to activation of mGluRs.

The tetanus patterns for the induction of long-term depression in the adult rat hippocampus / 生理学报

Previous reports suggested that a low-frequency stimulus (LFS) of 1~2 Hz (600~900 pulses) induced a homosynaptic long-term depression (LTD) of synaptic efficacy in the hippocampal CA1 area of young rats (< 4-week old). However, these stimulation protocols often failed to induce LTD in the adult CA1 hippocampus. In the present study, we examined the effects of two novel tetanus patterns on LTD induction in adult rat hippocampal slices. We determined that these novel stimulation protocols induced LTD in the adult hippocampus, and that the characteristics of induced LTD were parameter-specific, including latency (period from the end of tetanus to a beginning of LTD) and the amplitude of LTD. These results suggest that LFS with certain patterns can induce LTD in the CA1 area of adult rat hippocampal slices, and that the multi-trains of 2-Hz protocol provided more effective response than the 5-Hz protocol.

Changes in field excitatory postsynaptic potential and population spike in CA1 region of rat hippocampal slices following low-frequency stimulation / 生理学报

The technique of extracellular recording was used and the changes in the slope of field excitatory postsynaptic potential (S-EPSP) and the amplitude of population spike (A-PS) were observed when homosynaptic long-term depression (LTD) was induced by low-frequency stimulation (LFS) in the CA1 region of rat hippocampal slices. After LFS of 900 pulses at 1 Hz was delivered, S-EPSP and A-PS were reduced by 35.4 +/- 5.3% and 68.0 +/- 7.2%, respectively. When LFS of 450 pulses at 1 Hz was delivered, S-EPSP and A-PS were reduced by 14.3 +/- 2.3% and 36.8 +/- 6.7%, respectively. In both groups, the change in A-PS was significantly greater than that in S-EPSP (P<0.01). The changes in both indexes in the group of 900 pulses were greater than those in the group of 450 pulses (P<0.05). High Mg(2+) (4 mmol/L) could attenuate the synaptic transmission, but did not affect the induction of LTD. In the high Mg(2+) medium, the change in A-PS induced by LFS was also markedly greater than that in S-EPSP (P<0.01). These results indicate that the level of homosynaptic LTD induced by LFS is dependent not only on the numbers of pulses of LFS delivered, but also on the selection of evaluating index.