Propagation of activity-dependent synaptic depression in simple neural networks

Computational maps are of central importance to a neuronal representation of the outside world. In a map, neighboring neurons respond to similar sensory features. A well studied example is the computational map of interaural time differences (ITDs), which is essential to sound localization in a variety of species and allows resolution of ITDs of the order of 10 s. Nevertheless, it is unclear how such an orderly representation of temporal features arises. We address this problem by modeling the ontogenetic development of an ITD map in the laminar nucleus of the barn owl. We show how the owl's ITD map can emerge from a combined action of homosynaptic spike-based Hebbian learning and its propagation along the presynaptic axon. In spike-based Hebbian learning, synaptic strengths are modified according to the timing of pre-and postsynaptic action potentials. In unspecific axonal learning, a synapse's modification gives rise to a factor that propagates along the presynaptic axon and affects the properties of synapses at neighboring neurons. Our results indicate that both Hebbian learning and its presynaptic propagation are necessary for map formation in the laminar nucleus, but the latter can be orders of magnitude weaker than the former. We argue that the algorithm is important for the formation of computational maps, when, in particular, time plays a key role.C omputational maps (1, 2) transform information about the outside world into topographic neuronal representations. They are a key concept in information processing by the nervous system. Many results point to an ontogenetic development that is critically driven by sensory experience (3). Here we focus on the development of maps of exclusively temporal features (4-10), where the time course of stimuli carries relevant information, in contrast to previous studies that have shown the emergence of orderly representations of spatial or spatiotemporal features. A prominent example is the map of interaural time differences (ITDs) that is used for sound localization (11-13).Sound localization is important to the survival of many animal species-in particular, to those that hunt in the dark. ITDs often are used as a spatial cue. Because the range of available ITDs depends on the size of the head, ITDs are normally well below 1 ms; they can be measured with a precision of up to a few microseconds. In this article, we address the question of how temporal information from both ears can be transmitted to a site of comparison where neurons are tuned to ITDs, and how those ITD-tuned neurons can be organized in a map. A first step toward a solution was made by Jeffress (1) as early as 1948. He proposed a scheme (Fig. 1A) that combines axonal delay lines from both ears and neuronal coincidence detectors to convert ITDs into a place code where a spatial pattern of neuronal activity codes the ITD. His scheme has had a profound impact on understanding sound localization. Neurons tuned to ITDs and maps resembling the circuit envisioned by Jeffress have been observed in many animals...

Section: Discussionsupporting

confidence: 86%

“…39). Long-range cytoplasmic signaling within the presynaptic neuron can be responsible for the propagation of both long-term synaptic depression (35)(36)(37) and long-term synaptic potentiation (38). We call this mechanism ''nonspecific axonal learning.''…”

mentioning

confidence: 99%

Formation of temporal-feature maps by axonal propagation of synaptic learning

Kempter

Leibold

Wagner

et al. 2001

“…Low-density cultures of rat hippocampal neurons were transfected at 5 days in vitro (DIV5) with plasmids expressing Bcl-x L tagged at the N terminus with green fluorescent protein (GFP-Bcl-x L ) or the Mito-GFP control, in which the mitochondrial targeting sequence of COX4 is fused to GFP. At 12 days posttransfection (DIV17), neurons with green somata were voltage-clamped at their resting potential in the presence of 1 M tetrodotoxin to block action potentials (26), and miniature postsynaptic currents were recorded (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

“…They were distinguished by the slower decay time of mIPSPs and were sorted on a computer-based template by using pClamp 9.0 (Molecular Devices) according to ref. 26.…”

Section: Methodsmentioning

confidence: 99%

Bcl-x _L induces Drp1-dependent synapse formation in cultured hippocampal neurons

Li¹,

Chen

Jones³

et al. 2008

215

233

Maturation of neuronal synapses is thought to involve mitochondria. Bcl-xL protein inhibits mitochondria-mediated apoptosis but may have other functions in healthy adult neurons in which Bcl-xL is abundant. Here, we report that overexpression of Bcl-xL postsynaptically increases frequency and amplitude of spontaneous miniature synaptic currents in rat hippocampal neurons in culture. Bcl-xL, overexpressed either pre or postsynaptically, increases synapse number, the number and size of synaptic vesicle clusters, and mitochondrial localization to vesicle clusters and synapses, likely accounting for the changes in miniature synaptic currents. Conversely, knockdown of Bcl-xL or inhibiting it with ABT-737 decreases these morphological parameters. The mitochondrial fission protein, dynamin-related protein 1 (Drp1), is a GTPase known to localize to synapses and affect synaptic function and structure. The effects of Bcl-xL appear mediated through Drp1 because overexpression of Drp1 increases synaptic markers, and overexpression of the dominant-negative dnDrp1-K38A decreases them. Furthermore, Bcl-xL coimmunoprecipitates with Drp1 in tissue lysates, and in a recombinant system, Bcl-xL protein stimulates GTPase activity of Drp1. These findings suggest that Bcl-xL positively regulates Drp1 to alter mitochondrial function in a manner that stimulates synapse formation.Bcl-2 ͉ synaptic transmission ͉ mitochondria ͉ cell death ͉ ABT-737

“…In Xenopus nerve-muscle cultures, LTD induced at one neuromuscular synapse can spread to synapses made by the same neuron onto another myocyte, apparently by signaling within the neuronal cytoplasm, because rapid clearance of extracellular fluid does not prevent the spread of depression (135). In networks of cultured hippocampal neurons, LTD and LTP induced at glutamatergic synapses were found to spread retrogradely to the input synapses on the dendrites of the presynaptic neuron (backpropagation), as well as laterally to synapses made by divergent outputs of the presynaptic neuron (presynaptic lateral propagation) (136,137). Although presynaptic lateral propagation may be accounted for by the possibility of local spread of a diffusible retrograde signal between postsyn-aptic spines of different neurons sharing the same presynaptic bouton (''multisynapse'' bouton; see ref.…”

Section: Retrograde Signaling During Synaptogenesismentioning

confidence: 99%

Retrograde signaling at central synapses

Tao

Poo

2001

Self Cite

124

Transcellular retrograde signaling from the postsynaptic target cell to the presynaptic neuron plays critical roles in the formation, maturation, and plasticity of synaptic connections. We here review recent progress in our understanding of the retrograde signaling at developing central synapses. Three forms of potential retrograde signals-membrane-permeant factors, membrane-bound factors, and secreted factors-have been implicated at both developing and mature synapses. Although many of these signals may be active constitutively, retrograde factors produced in association with activity-dependent synaptic plasticity, e.g., long-term potentiation and long-term depression, are of particular interest, because they may induce modification of neuronal excitability and synaptic transmission, functions directly related to the processing and storage of information in the nervous system. N eural information coded by the action potential is transmitted through a chemical synapse in the anterograde direction by release of neurotransmitters, neuropeptides, and other protein factors from the presynaptic terminal. These molecules produce immediate changes in the membrane potential as well as long-term structural and metabolic changes in the postsynaptic cell. Over the past several decades, it has become increasingly clear that information exchange at the synapse is bidirectional: the postsynaptic cell also provides a variety of retrograde signals to the presynaptic neuron. This reciprocal interaction is crucial for the differentiation and maintenance of the presynaptic cell as well as the formation and maturation of the synapse. The general notion of retrograde signaling involves postsynaptic production of a signal, either constitutively or triggered by synaptic activity, that acts on the presynaptic neuron through the following mechanisms. First, the retrograde signal can be carried by a membrane-permeant molecule that diffuses across the plasma membranes from the postsynaptic cell directly into the presynaptic nerve terminal. Second, membraneimpermeant but soluble factors can be packaged and secreted via exocytotic vesicles by the postsynaptic cell and exert the retrograde action by binding and activation of receptors on the presynaptic membrane. Third, direct signaling through the synaptic cleft may be accomplished through mediation of physically coupled pre-and postsynaptic membrane-bound proteins, including transmembrane proteins as well as those secreted and immobilized in the extracellular matrix within the synaptic cleft. This review will summarize recent progress in the study of retrograde regulation at central synapses, with a focus on the role of retrograde interaction in the formation and activitydependent plasticity of synapses. Some aspects of this subject have been more extensively reviewed elsewhere (1). An excellent review of signaling at developing neuromuscular junctions (NMJs) has also appeared recently (2). Retrograde Signaling During SynaptogenesisOur present understanding of the process of synaptogenesis...