Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

Interaction of nicotinic acetylcholine receptors with dopamine receptors in synaptic plasticity of the mouse insular cortex

The insular cortex plays essential roles in nicotine addiction. However, much is still unknown about its cellular and synaptic mechanisms responsible for nicotine addiction. We have previously shown that in layer 5 pyramidal neurons of the mouse insular cortex, activation of the nicotinic acetylcholine receptors (nAChRs) suppresses synaptic potentiation through enhancing GABAergic synaptic transmission, although it enhances both glutamatergic and GABAergic synaptic transmission. In the present study, we examined whether dopamine receptors might contribute to the nicotine‐induced inhibition of synaptic potentiation. The nicotine‐induced inhibition of synaptic potentiation was decreased in the presence of a D1 dopamine receptor antagonist SCH23390 irrespective of the presence of a D2 dopamine receptor antagonist sulpiride, suggesting that D1 dopamine receptors are involved in nicotine‐induced inhibition. We also investigated how dopamine receptors might contribute to the nAChR‐induced enhancement of glutamatergic and GABAergic synaptic transmission. The nAChR‐induced enhancement of GABAergic synaptic transmission was decreased in the presence of SCH23390 irrespective of the presence of sulpiride, whereas that of glutamatergic synaptic transmission was not altered in the presence of SCH23390 and sulpiride. These results suggest that D1 dopamine receptors are involved in the nAChR‐induced enhancement of GABAergic synaptic transmission while dopamine receptors are not involved in that of glutamatergic synaptic transmission. These observations indicate that the interaction between nAChRs and D1 dopamine receptors plays critical roles in synaptic activities in layer 5 pyramidal neurons of the mouse insular cortex. These insular synaptic changes might be associated with nicotine addiction.     

Ultrastructural reversible changes in fish neuromuscular junctions after chronic exercise

Neuromuscular junctions (NJs) of fin muscles of teleostean fishes, Lebistes reticulatus, were ultrastructurally analyzed during 60 min of chronic exercise and a subsequent period of 90 min of induced recovery. NJs from 30-min-exercised fishes showed an almost complete depletion of synaptic vesicles (SVs), corresponding to 83% of SV consumption; 76% of axon terminals were branched at the end of this period. During the recovery period, it was possible to observe the reversibility of the changes induced by the exercise and the transitory events that lead to the reacquirement of the normal NJ morphology. After 15 min of rest, SV population increased to a value of 54.6 SVs/micron2 and the percentage of branched axons was 66.5%. At 60 min of recovery the number of SVs reached a value of 84.6 SVs/micron2. The SV population was fully reestablished at 80 min of rest, while the percentage of branched axons was found within normal ranges after 90 min of recovery. These results demonstrate that chronic exercise induced physiological depletion of NJ SVs and other axon terminal morphological changes, as well as that postexercise rest induces the reestablishment of the normal NJ morphology.     

Neuronal plasticity in memory and learning abilities: Theoretical position and selective review

Neural plasticity of modality-nonspecific and modality-specific memory and learning abilities pertains to fluid intelligence and crystallized intelligence, respectively. The limbic system with the novelty neurons of the hippocampus interacts with the prefrontal cortex optimization of the orienting reflex and voluntary attention. Brain-derived neurotrophic factor produced by novelty neurons of the hippocampus contributes to long-term memory formation and improves learning abilities in a wide range of disciplines. Synergistic combination of stimulation with “analytical-specific visual perceptual patterns” and “optimally high” physiological activation of the bilateral electrodermal system optimizes the limbic system and prefrontal cortex activity as demonstrated by enhanced prefrontal N450 ERPs to a memory workload paradigm. This is accompanied by improvements in auditory retention tasks, word memorization, higher school achievement and marks, and an amelioration of “analytical-specific perceptual skills” as measured by the Mangina-Test. Intracerebral ERPs to a memory workload paradigm contributed to the elucidation of limbic structures and neocortical sites involved in memory workload processes. The progressive degeneration of these same structures causes the gradual decline of memory functions observed in early Alzheimer's disease. Research findings indicate that ERPs elicited by a memory workload paradigm are sensitive markers for diagnosis, treatment and clinical follow-up of early Alzheimer's patients. In addition, ERPs provide objective measurement of cholinergic medication effects on cerebral functions involved in memory processes through neuropsychophysiological parameters.     

表皮生长因子对大鼠脑梗死后神经功能恢复的影响

目的 观察表皮生长因子（EGF）对大鼠脑梗死后神经功能恢复的影响。方法 采用肾血管性高血压大鼠制作一侧大脑中动脉皮层支闭塞（MCAO）模型。MCAO术后24 h，32只大鼠侧脑室注入10μl EGF（100μg/L），连续2d，共2μg（EGF组）；32只大鼠只注入不含EGF的等量溶液（对照组）。MCAO术后1、2、3和4w，行Bederson神经功能评分后，免疫印迹检测双侧大脑半球生长相关蛋白（GAP43）、突触囊泡蛋白（SYN）和胶质原纤维酸性蛋白（GFAP）的表达。结果 与同期对照组相比，EGF组大鼠在MCAO术后1、2w神经运动功能恢复更好，脑梗死灶同侧半球GAP43、SYN和GFAP有更早期和更高表达（P<0.05）。结论 GAP43、SYN和GFAP等蛋白的早期高峰表达可能与EGF引起的早期神经可塑性改善有关。     

Activity-dependent Decay of Early LTP Revealed by Dual EPSP Recording in Hippocampal Slices from Young Rats

The early maintenance of long-term potentiation (LTP) was studied in the CA1 region of hippocampal slices from 12- to 18-day-old rats in a low-magnesium solution (0.1 mM). The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated components of the field excitatory postsynaptic potential were estimated in parallel using early and late measurements of the composite potential. At the normal test stimulus frequency of 0.1 Hz, LTP was seen initially as a predominant increase in the AMPA component, but converted, via a substantial decay of this component and a gradual growth of the NMDA component, into nearly equal changes of the two components. Interrupting the test stimulation for 10 min, changing the test stimulus frequency to 1/60 Hz after LTP induction, or using a test stimulus frequency of 1/60 Hz during the entire experiment significantly reduced the decay of the potentiation of the AMPA component while enhancing the potentiation of the NMDA one. The ratio between the magnitudes of the two excitatory postsynaptic potential (EPSP) components showed a decaying time course that was independent of the manipulations used. Application of the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (50μM) after LTP induction stabilized the LTP of the AMPA component until washout was started. On the other hand, the phosphatase inhibitor okadaic acid (1 μM) resulted in decay of the potentiation of both EPSP components back to around baseline and altered the time course of the ratio between the components. Our results show that the early maintenance of LTP is controlled in an activity-dependent and NMDA-dependent manner. This process accelerates the decay of LTP of both AMPA and NMDA components in parallel, suggesting that it is similar to homosynaptic long-term depression, although it operates at the normal test stimulus frequency. The data support a scenario in which LTP ensues as a selective AMPA receptor modification and subsequently converts to another modification, possibly a presynaptic one.     

Long Fibre Growth by Axons of Embryonic Mouse Hippocampal Neurons Microtransplanted into the Adult Rat Fimbria

We have described a method for the microtransplantation of a suspension of a few thousand cells from mid to late embryonic mouse hippocampi into the fimbria of immunosuppressed adult rat hosts. There was close graft-to-host contact, across a non-scarred interface. The transplanted cells included CA3 type pyramids, and were enclosed within the host myelinated fibre tract, whose glial framework was largely undisturbed. Immunohistochemistry of two species-specific markers (M6 and Thy-1.2) showed that the donor mouse neurons grew fine (<0.5 μm diameter) axons which extended singly or in fascicles through the rat host fimbria for a maximum distance of at least 10 mm. The donor axons were intimately integrated among and closely aligned to the host tract axons and to the interfascicular glial rows of the host tract. The axons travelled (i) laterally through the ipsilateral fimbria, (ii) medially across the midline in the ventral hippocampal commissure to reach the contralateral fimbria and alveus, and (iii) rostro-medially to the septum. On approaching the terminal fields appropriate to hippocampal CA3 pyramidal cell axons, the transplant axons gave rise to fine preterminal branches which were continuous with a reticular or amorphous immunoreactivity in the stratum oriens and stratum pyramidale of the ipsilateral hippocampus, and in the lateral and triangular septal nuclei. The donor axons extended along the host fimbria at a rate of ∼ 1 mm per day, reaching their terminal field destinations by ∼1–2 weeks. At 7 weeks the projections were maintained, but with little further extension. These observations indicate that the microenvironment of myelinated adult fibre tracts is permissive for an abundant and rapid growth of axons from transplanted embryonic cell suspensions. These axons can leave host tracts to invade appropriate terminal fields.     

Flip side of synaptic plasticity: Long-term depression mechanisms in the hippocampus

There is growing interest in the phenomenon of long-term depression (LTD) of synaptic efficacy that, together with long-term potentiation (LTP), is a putative information storage mechanism in mammalian brain. In neural network models, multiple learning rules have been used for LTD induction. Similarly, in neurophysiological studies of hippocampal synaptic plasticity, a variety of activity patterns have been effective at inducing LTD, although experimental paradigms are still being optimized. In this review the authors summarize the major experimental paradigms and compare what is known about the mechanisms of LTD induction. Although all paradigms appear to initiate a cascade of events leading to an elevated level of Ca²⁺ postsynaptically, the extent to which these paradigms involve common expression mechanisms has not yet been tested. The authors discuss several critical experiments that would address this latter issue. Numerous questions about the properties and mechanisms of LTD(s) in the hippocampus remain to be answered, but it is clear that LTD has finally arrived, and will soon be attracting attention equal to its flip side, LTP. © 1994 Wiley-Liss, Inc.     

Age-related Changes in Excitability and Recurrent Inhibition in the Rat CA1 Hippocampal Region

In hippocampal slices from male Wistar rats aged 1–34 months, we recorded the synaptic field potential responses of the CA1 neurons to stimulation of Schaffer collaterals. Eight electrophysiological indexes were extracted from input/output curves and compared in 11 age groups from 1 to 30 months. Neuronal excitability presented a U-shaped curve of development with a minimum at ˜7–8 months of age. There was a significant continuous increase in neuronal excitability, i.e. a decrease in excitatory postsynaptic potential (EPSP) producing both the threshold and half-maximal population spike from middle age (8–10 months) to senescence (30 months). Synaptic efficiency also increased in old rats to reach a maximum during senescence, i.e. both the current for threshold EPSP and that for half-maximal EPSP reached a minimum in senescence, although the earlier developmental patterns of these two indexes were non-linear. The duration of the field EPSP elicited with maximal stimulation presented an abrupt decay after the first month. Aged animals presented a relatively small maximal population spike. Recurrent inhibition was most prominent on neuronal excitability rather than synaptic strength. Measured as the percentage change in the half-maximal EPSP and half-maximal population spike, recurrent inhibition was found to decrease during the first 7–10 months of life and remained small in later development.     

Adaptation of the disector method to rare small organelles in TEM sections exemplified by counting synaptic bodies in the rat pineal gland

The disector is the only objective method for quantifying particles of variable size in a given volume. With this method, cell organelles are identified on adjacent sections, but only those present in one section are counted. When counting extremely rare structures in transmission electron microscope sections (physical disector), the usual procedure of counting on electron micrographs is limited for economic reasons (e.g. micrographs highly outnumbering the investigated structures). Hence, to apply this unbiased stereological method, a modification of the physical disector concerning 3 aspects has been developed. (1) The prerequisite of screening large corresponding tissue areas (here ∼65000 μm²) was fulfilled by examining tissue areas along the edges of ultrathin sections. (2) The size of the counting frame was determined by measuring the lengths of the section margins (minus a guard area) by means of a Morphomat. This value was multiplied by the width of the investigated tissue zone, corresponding to the diameter of the electron microscope viewing screen. (3) Disector counting was carried out simultaneously on both sections (bidirectional disector) to improve efficiency. In the present study tiny synaptic bodies (SBs) were quantitated by disector in a rat pineal gland, yielding ∼30 SBs/1000 μm³. By contrast, single section profile counts of SBs amounted to 90 SBs/20000 μm². Since the presently described adaptation of the disector is time-consuming, it is proposed to determine a proportion factor allowing to estimate number of structures per volume based on single section profile counts. This would decrease the evaluation time by more than 50%.