Activity-dependent plasticity of synaptic efficacy at inhibitory junctions

Despite a considerable amount of investigation on long-term potentiation, the question of whether this process occurs at inhibitory synapses has remained controversial until studies of these junctions have been achieved in the Mauthner cell of Teleosts. In this preparation, inhibitory long-term potentiation similar to that occurring at hippocampal excitatory synapses has been demonstrated.     

Activity-dependent changes in cholinergic innervation of the mouse olfactory bulb

The interplay between olfactory activity and cholinergic modulation remains to be fully understood. This report examines the pattern of cholinergic innervation throughout the murine main olfactory bulb across different developmental stages and in naris-occluded animals. To visualize the pattern of cholinergic innervation, we used a transgenic mouse model, which expresses a fusion of the microtubule-associated protein, tau, with green fluorescence protein (GFP) under the control of the choline acetyltransferase (ChAT) promoter. This tau-GFP fusion product allows for a remarkably vivid and clear visualization of cholinergic innervation in the main olfactory bulb (MOB). Interestingly, we find an uneven distribution of GFP label in the adult glomerular layer (GL), where anterior, medial, and lateral glomerular regions of the bulb receive relatively heavier cholinergic innervation than other regions. In contrast to previous reports, we find a marked change in the pattern of cholinergic innervation to the GL following unilateral naris occlusion between the ipsilateral and contralateral bulbs in adult animals.     

Activity-dependent wiring of the developing hippocampal neuronal circuit

In the developing hippocampus, functional excitatory synaptic connections seem to be recruited from a preformed, initially silent synaptic network. This functional synapse induction requires presynaptic action potentials paired with postsynaptic depolarization, thus obeying Hebb's rule of association. During early postnatal development the hippocampus exhibits an endogenous form of patterned neuronal activity that is driven by GABAergic depolarization. We propose that this recurrent activity promotes the input-specific induction of functional synapses in the CA1 region. Thus, activity-dependent synaptic reorganization in the developing hippocampus appears to be dominated by an active recruitment of new synapses rather than an active elimination of redundant connections.     

昆虫嗅觉可塑性研究进展

嗅觉是昆虫的主要感觉模式,在昆虫的重要行为活动如寻找配偶、定位寄主、选择产卵场所等中起着关键作用。昆虫通过触角等外周嗅觉器官感受外界的化学信号并转化为电信号,电信号传输到中枢神经系统进行加工整合,最后通过大脑发出指令调控自身关键的行为。昆虫需要在合适的时机对不同气味作出反应,从而保证其能够在不同生理状态下完成特定的行为。这就要求昆虫的嗅觉系统具有可塑性,即根据不同的生理状态,如日龄、取食状态、交配、节律等对相同气味作出不同的反应。本文综述了不同生理状态对昆虫嗅觉行为和嗅觉神经系统的影响,以及昆虫嗅觉可塑性产生的机制,为加深和扩展人们对昆虫嗅觉系统的认识和建立新的害虫防控策略提供参考。     

Activity-dependent morphological synaptic plasticity in an adult neurosecretory system: magnocellular oxytocin neurons of the hypothalamus.

Oxytocin and vasopressin neurons, located in the supraoptic and paraventricular nuclei of the hypothalamus, send their axons to the neurohypophysis where the neurohormones are released directly into the general circulation. Hormone release depends on the electrical activity of the neurons, which in turn is regulated by different afferent inputs. During conditions that enhance oxytocin secretion (parturition, lactation, and dehydration), these afferents undergo morphological remodelling which results in an increased number of synapses contacting oxytocin neurons. The synaptic changes are reversible with cessation of stimulation. Using quantitative analyses on immunolabelled preparations, we have established that this morphological synaptic plasticity affects both inhibitory and excitatory afferent inputs to oxytocin neurons. This review describes such synaptic modifications, their functional significance, and the cellular mechanisms that may be responsible.     

Modulation of synaptic plasticity in the hippocampus and piriform cortex by physiologically meaningful olfactory cues in an olfactory association task

Animals were trained to discriminate two natural odors while another group was trained to discriminate between a patterned electrical stimulation distributed on the lateral olfactory tract (LOT), labelled olfaco-mimetic stimulation (OMS), used as an olfactory cue versus a natural odor. No statistically significant difference was observed in behavioral data between these two groups. The animals trained to learn the meaning of the OMS exhibited a gradual long-term potentiation (LTP) phenomenon in the piriform cortex. When a group of naive animals was pseudo-conditioned, giving the OMS for the same number of sessions but without any olfactory training, no LTP was recorded. These results indicate that the process of learning olfactory association gradually potentiates cortical synapses in a defined cortical terminal field, and may explain why LTP in the piriform cortex is not elicited by the patterned stimulation itself, but only in an associative context. As olfactory and hippocampus regions are connected via the lateral entorhinal cortex, the olfactomimetic model was used to study the dynamic of involvement of the dentate gyrus (DG) in learning and memory of this associative olfactory task. Polysynaptic field potentials, evoked by the LOT stimulation, were recorded in the molecular layer of the ipsilateral DG. An early and rapid (2nd session) potentiation was observed when a significant discrimination of the two cues began to be observed. The onset latency of the potentiated response was 30–40 ms. When a group of naive animals was pseudoconditioned, no change was observed. Taken together, these results support the hypothesis that early activation of the DG during the learning of olfactory cue allows the progressive storage of olfactory information in a defined set of potentiated cortical synapses. The onset latency of the polysynaptic potentiated responses suggests the existence of a reactivating hippocampal loops during the processing of olfactory information.     

A novel local circuit in the olfactory bulb involving an old short-axon cell

Many local circuit interactions in the olfactory bulb involve atypical dendrodendritic synapses. In this issue of Neuron, Pressler and Strowbridge report a functional analysis of a class of short-axon interneurons in the bulb called Blanes cells. Blanes cells make GABAergic axonal contacts onto granule cells and may mediate a form of local feedforward disinhibition.     

Developmental regulation of olfactory circuit formation in mice

In mammals, odorants induce various behavioral responses that are critical to the survival of the individual and species. Binding signals of odorants to odorant receptors (ORs) expressed in the olfactory epithelia are converted to an odor map, a pattern of activated glomeruli, in the olfactory bulb (OB). This topographic map is used to identify odorants for memory-based learned decisions. In the embryo, a coarse olfactory map is generated in the OB by a combination of dorsal-ventral and anterior-posterior targeting of olfactory sensory neurons (OSNs), using specific sets of axon-guidance molecules. During the process of OSN projection, odor signals are sorted into distinct odor qualities in separate functional domains in the OB. Odor information is then conveyed by the projection neurons, mitral/tufted cells, to various regions in the olfactory cortex, particularly to the amygdala for innate olfactory decisions. Although the basic architecture of hard-wired circuits is generated by a genetic program, innate olfactory responses are modified by neonatal odor experience in an activity-dependent manner. Stimulus-driven OR activity promotes post-synaptic events and dendrite selection in the responding glomeruli making them larger. As a result, enhanced odor inputs in neonates establish imprinted olfactory memory that induces attractive responses in adults, even when the odor quality is innately aversive. In this paper, I will provide an overview of the recent progress made in the olfactory circuit formation in mice.     

Activity-dependent adjustments of the inhibitory network in the olfactory bulb following early postnatal deprivation

The first-order sensory relay for olfactory processing, the main olfactory bulb (MOB), retains the ability to acquire new interneurons throughout life. It is therefore a particularly appropriate region for studying the role of experience in sculpting neuronal networks. We found that nostril closure decreased the number of newborn granule cells in the MOB, the complexity of their dendritic arborization, and their spine density, without affecting the preexisting population of granule cells. Accordingly, the frequency of miniature synaptic inhibitory events received by mitral cells was reduced. However, due to a compensatory increase in newborn granule cell excitability, action potential-dependent GABA release was dramatically enhanced, thus counteracting the reduction in spine density and leading to an unaltered synchronization of mitral cell firing activity. Together, this study reveals a unique form of adaptive response brought about exclusively by the cohort of newborn cells and used to maintain normal functioning of the MOB.     

Interhemispheric olfactory circuit and the memory beyond

In mammals, olfactory sensory neurons project their axons exclusively to the ipsilateral olfactory bulb. It remains unclear how odor information interacts between the two hemispheres of the brain. In this issue of Neuron, Yan et al. describe the precise interbulbar connection through the anterior olfactory nucleus pars externa (AONpE), which links contralateral isotypic olfactory columns.     

Morphological and functional plasticity of olfactory ensheathing cells

In the primary olfactory pathway, olfactory ensheathing cells (OECs) extend processes to envelop bundles of olfactory axons as they course towards their termination in the olfactory bulb. The expression of growth-promoting adhesion and extracellular matrix molecules by OECs, and their spatially close association with olfactory axons are consistent with OECs being involved in promoting and guiding olfactory axon growth. Because of this, OECs have been employed as a possible tool for inducing axonal regeneration in the injured adult CNS, resulting in significant functional recovery in some animal models and promising outcomes from early clinical applications. However, fundamental aspects of OEC biology remain unclear. This brief review discusses some of the experimental data that have resulted in conflicting views with regard to the identity of OECs. We present here recent findings which support the notion of OECs as a single but malleable phenotype which demonstrate extensive morphological and functional plasticity depending on the environmental stimuli. The review includes a discussion of the normal functional role of OECs in the developing primary olfactory pathway as well as their interaction with regenerating axons and reactive astrocytes in the novel environment of the injured CNS. The use of OECs to induce repair in the injured nervous system reflects the functional plasticity of these cells. Finally, we will explore the possibility that recent microarray data could point to OECs assuming an innate immune function or playing a role in modulating neuroinflammation.     

Regulation of spike timing-dependent plasticity of olfactory inputs in mitral cells in the rat olfactory bulb

The recent history of activity input onto granule cells (GCs) in the main olfactory bulb can affect the strength of lateral inhibition, which functions to generate contrast enhancement. However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory nerve (ON) inputs to mitral cells (MCs). Here we found that the repetitive stimulation of two distinct excitatory inputs to the GCs induced a persistent modification of lateral inhibition in MCs in opposing directions. This bidirectional modification of inhibitory inputs differentially regulated the subsequent synaptic plasticity of the excitatory ON inputs to the MCs, which was induced by the repetitive pairing of excitatory postsynaptic potentials (EPSPs) with postsynaptic bursts. The regulation of spike timing-dependent plasticity (STDP) was achieved by the regulation of the inter-spike-interval (ISI) of the postsynaptic bursts. This novel form of inhibition-dependent regulation of plasticity may contribute to the encoding or processing of olfactory information in the olfactory bulb.     

Profound context-dependent plasticity of mitral cell responses in olfactory bulb

On the basis of its primary circuit it has been postulated that the olfactory bulb (OB) is analogous to the retina in mammals. In retina, repeated exposure to the same visual stimulus results in a neural representation that remains relatively stable over time, even as the meaning of that stimulus to the animal changes. Stability of stimulus representation at early stages of processing allows for unbiased interpretation of incoming stimuli by higher order cortical centers. The alternative is that early stimulus representation is shaped by previously derived meaning, which could allow more efficient sampling of odor space providing a simplified yet biased interpretation of incoming stimuli. This study helps place the olfactory system on this continuum of subjective versus objective early sensory representation. Here we show that odor responses of the output cells of the OB, mitral cells, change transiently during a go–no-go odor discrimination task. The response changes occur in a manner that increases the ability of the circuit to convey information necessary to discriminate among closely related odors. Remarkably, a switch between which of the two odors is rewarded causes mitral cells to switch the polarity of their divergent responses. Taken together these results redefine the function of the OB as a transiently modifiable (active) filter, shaping early odor representations in behaviorally meaningful ways.     

Structural plasticity of olfactory neuropils in relation to insect diapause

1. Many insects that live in temperate zones spend the cold season in a state of dormancy, referred to as diapause. As the insect must rely on resources that were gathered before entering diapause, keeping a low metabolic rate is of utmost importance. Organs that are metabolically expensive to maintain, such as the brain, can therefore become a liability to survival if they are too large.
2. Insects that go through diapause as adults generally do so before entering the season of reproduction. This order of events introduces a conflict between maintaining low metabolism during dormancy and emerging afterward with highly developed sensory systems that improve fitness during the mating season.
3. We investigated the timing of when investments into the olfactory system are made by measuring the volumes of primary and secondary olfactory neuropils in the brain as they fluctuate in size throughout the extended diapause life‐period of adult Polygonia c‐album butterflies.
4. Relative volumes of both olfactory neuropils increase significantly during early adult development, indicating the importance of olfaction to this species, but still remain considerably smaller than those of nondiapausing conspecifics. However, despite butterflies being kept under the same conditions as before the dormancy, their olfactory neuropil volumes decreased significantly during the postdormancy period.
5. The opposing directions of change in relative neuropil volumes before and after diapause dormancy indicate that the investment strategies governing structural plasticity during the two life stages could be functionally distinct. As butterflies were kept in stimulus‐poor conditions, we find it likely that investments into these brain regions rely on experience‐expectant processes before diapause and experience‐dependent processes after diapause conditions are broken.
6. As the shift in investment strategies coincides with a hard shift from premating season to mating season, we argue that these developmental characteristics could be adaptations that mitigate the trade‐off between dormancy survival and reproductive fitness.

     

Studies of development and plasticity in the olfactory sensory neuron

The olfactory system is favorable for studying mechanisms of development, plasticity and regeneration. Monoclonal antibodies have been generated which differentially stain olfactory axons and can identify their earliest trajectories in the fetal rat. The developing olfactory pathway also shows differential metabolic activity, as revealed by the 2-deoxyglucose method, and these patterns show plasticity as judged by both physiological and behavioral measures. The sensory neurons undergo dieback and neurogenesis following axonal transection; electrophysiological methods are being used to reveal the membrane mechanisms underlying this unique capacity.     

Integrating synaptic plasticity and striatal circuit function in addiction

Exposure to addictive drugs causes changes in synaptic function within the striatal complex, which can either mimic or interfere with the induction of synaptic plasticity. These synaptic adaptations include changes in the nucleus accumbens (NAc), a ventral striatal subregion important for drug reward and reinforcement, as well as the dorsal striatum, which may promote habitual drug use. As the behavioral effects of drugs of abuse are long-lasting, identifying persistent changes in striatal circuits induced by in vivo drug experience is of considerable importance. Within the striatum, drugs of abuse have been shown to induce modifications in dendritic morphology, ionotropic glutamate receptors (iGluR) and the induction of synaptic plasticity. Understanding the detailed molecular mechanisms underlying these changes in striatal circuit function will provide insight into how drugs of abuse usurp normal learning mechanisms to produce pathological behavior.