Receptive field plasticity of neurons in rat auditory cortex

Using conventional electrophysiological technique, we investigated the plasticity of the frequency receptive fields (RF) of auditory cortex (AC) neurons in rats. In the AC, when the frequency difference between conditioning stimulus frequency (CSF) and the best frequency (BF) was in the range of 1--4 kHz, the frequency RF of AC neurons shifted. The smaller the differences between CSF and BF, the higher the probability of the RF shift and the greater the degree of the RF shift. To some extent, the plasticity of RF was dependent on the duration of the session of conditioning stimulus (CS). When the frequency difference between CSF and BF was bigger, the duration of the CS session needed to induce the plasticity was longer. The recovery time course of the frequency RF showed opposite changes after CS cessation.The RF shift could be induced by the frequency that was either higher or lower than the control BF, demonstrating no clear directional preference. The frequency RF of some neurons showed bidirectional shift, and the RF of other neurons showed single directional shift. The results suggest that the frequency RF plasticity of AC neurons could be considered asan ideal model for studying plasticity mechanism. The present study also provides important evidence for further study of learning and memory in auditory system.     

Parietal cortex contributions to information granules following memory consolidation

Previous studies have focused on changes in cerebral cortex activity accompanying memory formation and consolidation. Although the role of the parietal cortex in memory retrieval is well established, it is not well understood how parietal cortex memory con-solidation for mathematical rules is related to granularity of stored information (i.e., degree of detail or precision). Changes in parietal cortex activity associated with memory consolidation were analyzed using the Ebbinghaus paradigm and functional magnetic resonance imaging (fMRI). Over the course of 1 week, participants learned Boolean arithmetic tasks involving stimulus-response mapping rules containing either low- or high-granularity information. FMRI images were collected on day 1 (i.e., low-granularity condition) and day 7 (i.e., high-granularity condition). The present data suggested that with practice, stored information was converted from a low-granularity to a high-granularity form. By following rule learning, it was hypothesized that the process of consolidation would involve an increased degree of rule representation granularity. Evidence for this process was reflected in parietal cortex activity. This finding was consistent with the hypothesis that mnemonic reconstruction in the parietal cortex is required for memory consolidation, and results suggested that information granules are formed during memory consolidation. The present results could increase the understanding of the relationship between memory consolidation and information granularity.     

Ocular dominance plasticity in adult cat visual cortex after transplantation of cultured astrocytes

During a critical restricted period of postnatal development, the visual cortical circuitry is susceptible to modifications that are dependent on experience. If vision is restricted to only one eye during this period, the territories innervated by the deprived eye shrink considerably, whereas those innervated by the non-deprived eye expand, and the deprived eye loses the ability to influence almost all of the cells in the cortex. Thus, changes in ocular dominance are paralleled and possibly mediated by synapse elimination and axonal sprouting. Hypotheses about the mechanisms underlying ocular-dominance plasticity assume the activation of NMDA (N-methyl-D-aspartate) receptors and subsequent calcium influx as a trigger of synaptic modifications. In addition, plasticity relies on functional neuromodulatory afferents. On the basis of immunocytochemical studies, it was recently proposed that the presence of immature astrocytes is a prerequisite for visual cortical plasticity, and that the end of the critical period is causally linked to the maturation of astrocytes. Here we report, in support of this hypothesis, that resupplementation of the visual cortex of adult cats with astrocytes cultured from the visual cortex of newborn kittens reinduces ocular-dominance plasticity in adult animals.     

Structural basis of long-term potentiation in single dendritic spines

Dendritic spines of pyramidal neurons in the cerebral cortex undergo activity-dependent structural remodelling that has been proposed to be a cellular basis of learning and memory. How structural remodelling supports synaptic plasticity, such as long-term potentiation, and whether such plasticity is input-specific at the level of the individual spine has remained unknown. We investigated the structural basis of long-term potentiation using two-photon photolysis of caged glutamate at single spines of hippocampal CA1 pyramidal neurons. Here we show that repetitive quantum-like photorelease (uncaging) of glutamate induces a rapid and selective enlargement of stimulated spines that is transient in large mushroom spines but persistent in small spines. Spine enlargement is associated with an increase in AMPA-receptor-mediated currents at the stimulated synapse and is dependent on NMDA receptors, calmodulin and actin polymerization. Long-lasting spine enlargement also requires Ca2+/calmodulin-dependent protein kinase II. Our results thus indicate that spines individually follow Hebb's postulate for learning. They further suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long-term memory.     

Context-enabled learning in the human visual system

Training was found to improve the performance of humans on a variety of visual perceptual tasks. However, the ability to detect small changes in the contrast of simple visual stimuli could not be improved by repetition. Here we show that the performance of this basic task could be modified after the discrimination of the stimulus contrast was practised in the presence of similar laterally placed stimuli, suggesting a change in the local neuronal circuit involved in the task. On the basis of a combination of hebbian and anti-hebbian synaptic learning rules compatible with our results, we propose a mechanism of plasticity in the visual cortex that is enabled by a change in the context.     

A synaptic memory trace for cortical receptive field plasticity

Receptive fields of sensory cortical neurons are plastic, changing in response to alterations of neural activity or sensory experience. In this way, cortical representations of the sensory environment can incorporate new information about the world, depending on the relevance or value of particular stimuli. Neuromodulation is required for cortical plasticity, but it is uncertain how subcortical neuromodulatory systems, such as the cholinergic nucleus basalis, interact with and refine cortical circuits. Here we determine the dynamics of synaptic receptive field plasticity in the adult primary auditory cortex (also known as AI) using in vivo whole-cell recording. Pairing sensory stimulation with nucleus basalis activation shifted the preferred stimuli of cortical neurons by inducing a rapid reduction of synaptic inhibition within seconds, which was followed by a large increase in excitation, both specific to the paired stimulus. Although nucleus basalis was stimulated only for a few minutes, reorganization of synaptic tuning curves progressed for hours thereafter: inhibition slowly increased in an activity-dependent manner to rebalance the persistent enhancement of excitation, leading to a retuned receptive field with new preference for the paired stimulus. This restricted period of disinhibition may be a fundamental mechanism for receptive field plasticity, and could serve as a memory trace for stimuli or episodes that have acquired new behavioural significance.     

Sensory experience modifies the short-term dynamics of neocortical synapses.

Many representations of sensory stimuli in the neocortex are arranged as topographic maps. These cortical maps are not fixed, but show experience-dependent plasticity. For instance, sensory deprivation causes the cortical area representing the deprived sensory input to shrink, and neighbouring spared representations to enlarge, in somatosensory, auditory or visual cortex. In adolescent and adult animals, changes in cortical maps are most noticeable in the supragranular layers at the junction of deprived and spared cortex. However, the cellular mechanisms of this experience-dependent plasticity are unclear. Long-term potentiation and depression have been implicated, but have not been proven to be necessary or sufficient for cortical map reorganization. Short-term synaptic dynamics have not been considered. We developed a brain slice preparation involving rat whisker barrel cortex in vitro. Here we report that sensory deprivation alters short-term synaptic dynamics in both vertical and horizontal excitatory pathways within the supragranular cortex. Moreover, modifications of horizontal pathways amplify changes in the vertical inputs. Our findings help to explain the functional cortical reorganization that follows persistent changes of sensory experience.     

Foci of orientation plasticity in visual cortex

Cortical areas are generally assumed to be uniform in their capacity for adaptive changes or plasticity. Here we demonstrate, however, that neurons in the cat striate cortex (V1) show pronounced adaptation-induced short-term plasticity of orientation tuning primarily at specific foci. V1 neurons are clustered according to their orientation preference in iso-orientation domains that converge at singularities or pinwheel centres. Although neurons in pinwheel centres have similar orientation tuning and responses to those in iso-orientation domains, we find that they differ markedly in their capacity for adaptive changes. Adaptation with an oriented drifting grating stimulus alters responses of neurons located at and near pinwheel centres to a broad range of orientations, causing repulsive shifts in orientation preference and changes in response magnitude. In contrast, neurons located in iso-orientation domains show minimal changes in their tuning properties after adaptation. The anisotropy of adaptation-induced orientation plasticity is probably mediated by inhomogeneities in local intracortical interactions that are overlaid on the map of orientation preference in V1.     

谷氨酸能神经传递系统研究进展

谷氨酸广布于大脑皮质等处,以(-酮戊二酸、谷氨酰胺或鸟氨酸等为前体进行合成,通过快突触传递或慢突触传递与突触后膜上的三种类型的受体相结合,参与学习记忆、突触可塑性、细胞凋亡、自主运动神经活动及神经毒性作用等生理和病理功能。     

Neuroscience: rewiring the adult brain

Any analysis of plastic reorganization at a neuronal locus needs a veridical measure of changes in the functional output--that is, spiking responses of the neurons in question. In a study of the effect of retinal lesions on adult primary visual cortex (V1), Smirnakis et al. propose that there is no cortical reorganization. Their results are based, however, on BOLD (blood-oxygen-level-dependent) fMRI (functional magnetic resonance imaging), which provides an unreliable gauge of spiking activity. We therefore question their criterion for lack of plasticity, particularly in the light of the large body of earlier work that demonstrates cortical plasticity.     

利用基因芯片检测大鼠衰老相关的记忆障碍的调控基因

许多证据表明,正常衰老过程伴随着记忆力的衰退.但有些动物却不表现出这种年龄相关的记忆障碍.为了检测其中的分子机制,将24个月的老年大鼠按在水迷宫中的行为表现分成记忆损伤组和记忆未损伤组,分别取海马和内嗅皮层进行基因芯片检测.结果显示,在海马和内嗅皮层中分别有47和37个基因的表达发生了显著变化.但两个脑区的基因表达变化...     

Reduction in number of immunostained GABAergic neurones in deprived-eye dominance columns of monkey area 17

The primary visual cortex (area 17) of the Old World monkey is divided into alternating right- and left-eye dominance columns that are highly modifiable by visual experience during a critical period in development but display little morphological or physiological plasticity during adult life. However, changes in immunocytochemical staining for a calcium/calmodulin-dependent protein kinase occur in visual cortical neurones of adult monkeys after brief monocular deprivation and concentrations of putative neurotransmitters or their related enzymes can be altered with changes in neuronal activity in other systems. We therefore examined the effects of monocular deprivation on the immunocytochemical staining for gamma-aminobutyric acid (GABA) and its synthetic enzyme, glutamic acid decarboxylase (GAD), in adult monkey area 17. The staining for GABA and GAD in neuronal somata and terminals was markedly reduced within ocular dominance columns associated with a removed or a visually deprived eye, suggesting that the GABA concentration in cortical neurones may depend on their levels of activity. Thus area 17 of adult monkeys may retain a greater degree of plasticity than previously recognized and sensory experience can profoundly affect transmitter levels, in the cortex, apparently by regulating levels of a synthetic enzyme.     

Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex

Do new synapses form in the adult cortex to support experience-dependent plasticity? To address this question, we repeatedly imaged individual pyramidal neurons in the mouse barrel cortex over periods of weeks. We found that, although dendritic structure is stable, some spines appear and disappear. Spine lifetimes vary greatly: stable spines, about 50% of the population, persist for at least a month, whereas the remainder are present for a few days or less. Serial-section electron microscopy of imaged dendritic segments revealed retrospectively that spine sprouting and retraction are associated with synapse formation and elimination. Experience-dependent plasticity of cortical receptive fields was accompanied by increased synapse turnover. Our measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits.     

Synaptic computation

Neurons are often considered to be the computational engines of the brain, with synapses acting solely as conveyers of information. But the diverse types of synaptic plasticity and the range of timescales over which they operate suggest that synapses have a more active role in information processing. Long-term changes in the transmission properties of synapses provide a physiological substrate for learning and memory, whereas short-term changes support a variety of computations. By expressing several forms of synaptic plasticity, a single neuron can convey an array of different signals to the neural circuit in which it operates.     

Analysis of a spatial orientation memory in Drosophila

Flexible goal-driven orientation requires that the position of a target be stored, especially in case the target moves out of sight. The capability to retain, recall and integrate such positional information into guiding behaviour has been summarized under the term spatial working memory. This kind of memory contains specific details of the presence that are not necessarily part of a long-term memory. Neurophysiological studies in primates indicate that sustained activity of neurons encodes the sensory information even though the object is no longer present. Furthermore they suggest that dopamine transmits the respective input to the prefrontal cortex, and simultaneous suppression by GABA spatially restricts this neuronal activity. Here we show that Drosophila melanogaster possesses a similar spatial memory during locomotion. Using a new detour setup, we show that flies can remember the position of an object for several seconds after it has been removed from their environment. In this setup, flies are temporarily lured away from the direction towards their hidden target, yet they are thereafter able to aim for their former target. Furthermore, we find that the GABAergic (stainable with antibodies against GABA) ring neurons of the ellipsoid body in the central brain are necessary and their plasticity is sufficient for a functional spatial orientation memory in flies. We also find that the protein kinase S6KII (ignorant) is required in a distinct subset of ring neurons to display this memory. Conditional expression of S6KII in these neurons only in adults can restore the loss of the orientation memory of the ignorant mutant. The S6KII signalling pathway therefore seems to be acutely required in the ring neurons for spatial orientation memory in flies.     

离子型谷氨酸受体对海马突触传递长时程增强的影响

海马是完成学习与记忆活动的神经基础,海马部位突触可塑性增强与学习记忆有着密不可分的关系,而这种可塑性的增强主要是以谷氨酸为神经递质的,因此本文就有关海马部位突触可塑性增强与离子型谷氨酸受体的联系进行了阐述．     

Locally dynamic synaptic learning rules in pyramidal neuron dendrites

Long-term potentiation (LTP) of synaptic transmission underlies aspects of learning and memory. LTP is input-specific at the level of individual synapses, but neural network models predict interactions between plasticity at nearby synapses. Here we show in mouse hippocampal pyramidal cells that LTP at individual synapses reduces the threshold for potentiation at neighbouring synapses. After input-specific LTP induction by two-photon glutamate uncaging or by synaptic stimulation, subthreshold stimuli, which by themselves were too weak to trigger LTP, caused robust LTP and spine enlargement at neighbouring spines. Furthermore, LTP induction broadened the presynaptic-postsynaptic spike interval for spike-timing-dependent LTP within a dendritic neighbourhood. The reduction in the threshold for LTP induction lasted approximately 10 min and spread over approximately 10 microm of dendrite. These local interactions between neighbouring synapses support clustered plasticity models of memory storage and could allow for the binding of behaviourally linked information on the same dendritic branch.     

Potentiation of cortical inhibition by visual deprivation

The fine-tuning of circuits in sensory cortex requires sensory experience during an early critical period. Visual deprivation during the critical period has catastrophic effects on visual function, including loss of visual responsiveness to the deprived eye, reduced visual acuity, and loss of tuning to many stimulus characteristics. These changes occur faster than the remodelling of thalamocortical axons, but the intracortical plasticity mechanisms that underlie them are incompletely understood. Long-term depression of excitatory intracortical synapses has been proposed as a general candidate mechanism for the loss of cortical responsiveness after visual deprivation. Alternatively (or in addition), the decreased ability of the deprived eye to activate cortical neurons could be due to enhanced intracortical inhibition. Here we show that visual deprivation leaves excitatory connections in layer 4 (the primary input layer to cortex) unaffected, but markedly potentiates inhibitory feedback between fast-spiking basket cells (FS cells) and star pyramidal neurons (star pyramids). Further, a previously undescribed form of long-term potentiation of inhibition (LTPi) could be induced at synapses from FS cells to star pyramids, and was occluded by previous visual deprivation. These data suggest that potentiation of inhibition is a major cellular mechanism underlying the deprivation-induced degradation of visual function, and that this form of LTPi is important in fine-tuning cortical circuitry in response to visual experience.