Neural Systems & Circuits - Most accessed articles

Distributed network organization underlying feeding behavior in the mollusk Lymnaea

Paul Benjamin — 2012-04-17T00:00:00Z

The aim of the work reviewed here is to relate the properties of individual neurons to network organization and behavior using the feeding system of the gastropod mollusk, Lymnaea. Food ingestion in this animal involves sequences of rhythmic biting movements that are initiated by the application of a chemical food stimulus to the lips and esophagus. We investigated how individual neurons contribute to various network functions that are required for the generation of feeding behavior such as rhythm generation, initiation ('decision making'), modulation and hunger and satiety. The data support the view that feeding behavior is generated by a distributed type of network organization with individual neurons often contributing to more than one network function, sharing roles with other neurons. Multitasking in a distributed type of network would be 'economically' sensible in the Lymnaea feeding system where only about 100 neurons are available to carry out a variety of complex tasks performed by millions of neurons in the vertebrate nervous system. Having complementary and potentially alternative mechanisms for network functions would also add robustness to what is a 'noisy' network where variable firing rates and synaptic strengths are commonly encountered in electrophysiological recording experiments.

Epigenetic remodelling of brain, body and behaviour during phase change in locusts

Malcolm Burrows — 2011-07-26T00:00:00Z

The environment has a central role in shaping developmental trajectories and determining the phenotype so that animals are adapted to the specific conditions they encounter. Epigenetic mechanisms can have many effects, with changes in the nervous and musculoskeletal systems occurring at different rates. How is the function of an animal maintained whilst these transitions happen? Phenotypic plasticity can change the ways in which animals respond to the environment and even how they sense it, particularly in the context of social interactions between members of their own species. In the present article, we review the mechanisms and consequences of phenotypic plasticity by drawing upon the desert locust as an unparalleled model system. Locusts change reversibly between solitarious and gregarious phases that differ dramatically in appearance, general physiology, brain function and structure, and behaviour. Solitarious locusts actively avoid contact with other locusts, but gregarious locusts may live in vast, migrating swarms dominated by competition for scarce resources and interactions with other locusts. Different phase traits change at different rates: some behaviours take just a few hours, colouration takes a lifetime and the muscles and skeleton take several generations. The behavioural demands of group living are reflected in gregarious locusts having substantially larger brains with increased space devoted to higher processing. Phase differences are also apparent in the functioning of identified neurons and circuits. The whole transformation process of phase change pivots on the initial and rapid behavioural decision of whether or not to join with other locusts. The resulting positive feedback loops from the presence or absence of other locusts drives the process to completion. Phase change is accompanied by dramatic changes in neurochemistry, but only serotonin shows a substantial increase during the critical one- to four-hour window during which gregarious behaviour is established. Blocking the action of serotonin or its synthesis prevents the establishment of gregarious behaviour. Applying serotonin or its agonists promotes the acquisition of gregarious behaviour even in a locust that has never encountered another locust. The analysis of phase change in locusts provides insights into a feedback circuit between the environment and epigenetic mechanisms and more generally into the neurobiology of social interaction.

Simultaneous two-photon activation of presynaptic cells and calcium imaging in postsynaptic dendritic spines

Masanori Matsuzaki — 2011-01-26T00:00:00Z

Background: Dendritic spines of pyramidal neurons are distributed along the complicated structure of the dendritic branches and possess a variety of morphologies associated with synaptic strength. The location and structure of dendritic spines determine the extent of synaptic input integration in the postsynaptic neuron. However, how spine location or size relates to the position of innervating presynaptic cells is not yet known. This report describes a new method that represents a first step toward addressing this issue. Results: The technique combines two-photon uncaging of glutamate over a broad area (~500 × 250 × 100 μm) with two-photon calcium imaging in a narrow region (~50 × 10 × 1 μm). The former was used for systematic activation of layer 2/3 pyramidal cells in the rat motor cortex, while the latter was used to detect the dendritic spines of layer 5 pyramidal cells that were innervated by some of the photoactivated cells. This technique allowed identification of various sizes of innervated spine located <140 μm laterally from the postsynaptic soma. Spines distal to their parent soma were preferentially innervated by cells on the ipsilateral side. No cluster of neurons innervating the same dendritic branch was detected. Conclusions: This new method will be a powerful tool for clarifying the microarchitecture of synaptic connections, including the positional and structural characteristics of dendritic spines along the dendrites.

From Baconian to Popperian Neuroscience

David Gamez — 2012-01-30T00:00:00Z

The development of neuroscience over the past 50 years has some similarities with the development of physics in the 17th century. Towards the beginning of that century, Bacon promoted the systematic gathering of experimental data and the induction of scientific truth; towards the end, Newton expressed his principles of gravitation and motion in a concise set of mathematical equations that made precise falsifiable predictions. This paper expresses the opinion that as neuroscience comes of age, it needs to move away from amassing large quantities of data about the brain, and adopt a popperian model in which theories are developed that can make strong falsifiable predictions and guide future experimental work.

Q&A: What is the Open Connectome Project?

Joshua Vogelstein — 2011-11-18T00:00:00Z

Although it has been over a century since neuroscientists first conjectured that networks of neurons comprise the brain, technology has limited high-throughput investigations of neural circuitry until very recently. In the last couple of decades, several experimental paradigms have arisen that are poised to finally begin studying neuroanatomy in a high-throughput fashion. In 2005, the term connectome was coined independently by Patric Hagmann and Olaf Sporns, to describe the complete set of neural connections in a brain. Interestingly, both usages seemed to be referring to using Magnetic Resonance Imaging (MRI) to study human brain networks. Shortly thereafter, Narayanan "Bobby" Kasthuri and Jeff Lichtman published an article suggesting that "connectome" should refer to connections between neurons, which one can infer using Electron Microscopy (EM) and fluorescence microscopy (e.g., brainbow animals). "Projectome", they suggested, is more appropriate for MRI based studies. Yet, the word connectome stuck, and now refers to essentially any neuroscientific investigation of the relationship between (collections of) neurons, be they functional or structural.

Identification and analysis of a glutamatergic local interneuron lineage in the adult Drosophila olfactory system

Abhijit Das — 2011-01-26T00:00:00Z

Background: The antennal lobe of Drosophila is perhaps one of the best understood neural circuits, because of its well-described anatomical and functional organization and ease of genetic manipulation. Olfactory lobe interneurons - key elements of information processing in this network - are thought to be generated by three identified central brain neuroblasts, all of which generate projection neurons. One of these neuroblasts, located lateral to the antennal lobe, also gives rise to a population of local interneurons, which can either be inhibitory (GABAergic) or excitatory (cholinergic). Recent studies of local interneuron number and diversity suggest that additional populations of this class of neurons exist in the antennal lobe. This implies that other, as yet unidentified, neuroblast lineages may contribute a substantial number of local interneurons to the olfactory circuitry of the antennal lobe. Results: We identified and characterized a novel glutamatergic local interneuron lineage in the Drosophila antennal lobe. We used MARCM (mosaic analysis with a repressible cell marker) and dual-MARCM clonal analysis techniques to identify this novel lineage unambiguously, and to characterize interneurons contained in the lineage in terms of structure, neurotransmitter identity, and development. We demonstrated the glutamatergic nature of these interneurons by immunohistochemistry and use of an enhancer-trap strain, which reports the expression of the Drosophila vesicular glutamate transporter (DVGLUT). We also analyzed the neuroanatomical features of these local interneurons at single-cell resolution, and documented the marked diversity in their antennal lobe glomerular innervation patterns. Finally, we tracked the development of these dLim-1 and Cut positive interneurons during larval and pupal stages. Conclusions: We have identified a novel neuroblast lineage that generates neurons in the antennal lobe of Drosophila. This lineage is remarkably homogeneous in three respects. All of the progeny are local interneurons, which are uniform in their glutamatergic neurotransmitter identity, and form oligoglomerular or multiglomerular innervations within the antennal lobe. The identification of this novel lineage and the elucidation of the innervation patterns of its local interneurons (at single cell resolution) provides a comprehensive cellular framework for emerging studies on the formation and function of potentially excitatory local interactions in the circuitry of the Drosophila antennal lobe.

Dynamic development of the first synapse impinging on adult-born neurons in the olfactory bulb circuit

Hiroyuki Katagiri — 2011-02-01T00:00:00Z

The olfactory bulb (OB) receives and integrates newborn interneurons throughout life. This process is important for the proper functioning of the OB circuit and consequently, for the sense of smell. Although we know how these new interneurons are produced, the way in which they integrate into the pre-existing ongoing circuits remains poorly documented. Bearing in mind that glutamatergic inputs onto local OB interneurons are crucial for adjusting the level of bulbar inhibition, it is important to characterize when and how these inputs from excitatory synapses develop on newborn OB interneurons. We studied early synaptic events that lead to the formation and maturation of the first glutamatergic synapses on adult-born granule cells (GCs), the most abundant subtype of OB interneuron. Patch-clamp recordings and electron microscopy (EM) analysis were performed on adult-born interneurons shortly after their arrival in the adult OB circuits. We found that both the ratio of N-methyl-D-aspartate receptor (NMDAR) to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and the number of functional release sites at proximal inputs reached a maximum during the critical period for the sensory-dependent survival of newborn cells, well before the completion of dendritic arborization. EM analysis showed an accompanying change in postsynaptic density shape during the same period of time. Interestingly, the latter morphological changes disappeared in more mature newly-formed neurons, when the NMDAR to AMPAR ratio had decreased and functional presynaptic terminals expressed only single release sites. Together, these findings show that the first glutamatergic inputs to adult-generated OB interneurons undergo a unique sequence of maturation stages.

Functional connectivity in a rhythmic inhibitory circuit using Granger causality

Tilman Kispersky — 2011-05-25T00:00:00Z

Background: Understanding circuit function would be greatly facilitated by methods that allow the simultaneous estimation of the functional strengths of all of the synapses in the network during ongoing network activity. Towards that end, we used Granger causality analysis on electrical recordings from the pyloric network of the crab Cancer borealis, a small rhythmic circuit with known connectivity, and known neuronal intrinsic properties. Results: Granger causality analysis reported a causal relationship where there is no anatomical correlate because of the strong oscillatory behavior of the pyloric circuit. Additionally, we failed to find a direct relationship between synaptic strength and Granger causality in a set of pyloric circuit models. Conclusions: We conclude that the lack of a relationship between synaptic strength and functional connectivity occurs because Granger causality essentially collapses the direct contribution of the synapse with the intrinsic properties of the postsynaptic neuron. We suggest that the richness of the dynamical properties of most biological neurons complicates the simple interpretation of the results of functional connectivity analyses using Granger causality.

A novel, jitter-based method for detecting and measuring spike synchrony and quantifying temporal firing precision

Ariel Agmon — 2012-05-02T00:00:00Z

Background: Precise spike synchrony, at the millisecond or even sub-millisecond time scale, has been reported in different brain areas, but its neurobiological meaning and its underlying mechanisms remain unknown or controversial. Studying these questions is complicated by the lack of a validated, well-normalized and robust index for quantifying synchrony. Previously used measures of synchrony are often improperly normalized and thereby are not comparable between different experimental conditions, are sensitive to variations in firing rate or to the firing rate differential between the two neurons, and/or rely on untenable assumptions of firing rate stationarity and Poisson statistics. I describe here a novel measure, the Jitter-Based Synchrony Index (JBSI), that overcomes these issues.Results and discussionThe JBSI method is based on the introduction of virtual spike jitter. While previous implementations of the jitter method used it only to detect synchrony, the JBSI method also quantifies synchrony. Previous implementations of the jitter method used computationally intensive Monte Carlo simulations to generate surrogate spike trains, whereas the JBSI is computed analytically. The JBSI method does not assume any specific firing model, and does not require that the spike trains be locked to a repeating external stimulus. The JBSI can assume values from 1 (maximal possible synchrony) to -1 (minimal possible synchrony) and is therefore properly normalized. Using simulated Poisson spike trains with introduced controlled spike coincidences, I demonstrate that the JBSI is a linear measure of the spike coincidence rate, is independent of the mean firing frequency or the firing frequency differential between the two neurons, and is not sensitive to co-modulations in the firing rates of the two neurons. In contrast, several commonly used synchrony indices fail under one or more of these scenarios. I also demonstrate how the JBSI can be used to estimate the spike timing precision in the system. Conclusions: The JBSI is a conceptually simple and computationally efficient method that can be used to compute the statistical significance of firing synchrony, to quantify synchrony as a well-normalized index, and to estimate the degree of temporal precision in the system.

Genetic visualization of the secondary olfactory pathway in Tbx21 transgenic mice

Sachiko Mitsui — 2011-02-01T00:00:00Z

Background: Mitral and tufted cells are the projection neurons in the olfactory bulb, conveying odour information to various regions of the olfactory cortex. In spite of their functional importance, there are few molecular and genetic tools that can be used for selective labelling or manipulation of mitral and tufted cells. Tbx21 was first identified as a T-box family transcription factor regulating the differentiation and function of T lymphocytes. In the brain, Tbx21 is specifically expressed in mitral and tufted cells of the olfactory bulb. Results: In this study, we performed a promoter/enhancer analysis of mouse Tbx21 gene by comparing nucleotide sequence similarity of Tbx21 genes among several mammalian species and generating transgenic mouse lines with various lengths of 5' upstream region fused to a fluorescent reporter gapVenus. We identified the cis-regulatory enhancer element (~300 nucleotides) at ~ 3.0 kb upstream of the transcription start site of Tbx21 gene, which is both necessary and sufficient for transgene expression in mitral and tufted cells. In contrast, the 2.6-kb 5'-flanking region of mouse Tbx21 gene induced transgene expression with variable patterns in restricted populations of neurons predominantly located along the olfactory pathway. Furthermore, we generated transgenic mice expressing the genetically-encoded fluorescent exocytosis indicator, synaptopHluorin, in mitral and tufted cells for visualization of presynaptic neural activities in the piriform cortex. Conclusions: The transcriptional enhancer of Tbx21 gene provides a powerful tool for genetic manipulations of mitral and tufted cells in studying the development and function of the secondary olfactory pathways from the bulb to the cortex.