Frontiers in Neural Circuits

Publications in this journal

• Article: Three-dimensional tracking and analysis of ion channel signals across dendritic arbors.

  Ginger M, Broser P, Frick A
  [show abstract] [hide abstract]
  ABSTRACT: Most neuron types possess elaborate dendritic arbors that receive and integrate excitatory and inhibitory inputs from numerous other neurons to give rise to cell-type specific firing patterns. The computational properties of these dendrites are therefore crucial for neuronal information processing, and are strongly determined by the expression of many types of voltage-gated ion channels in their membrane. The dendritic distribution patterns of these ion channels are characteristic for each ion channel type, are dependent on the neuronal identity, and can be modified in a plastic or pathophysiological manner. We present a method that enables us to semi-automatically map and quantify in 3D the expression levels of specific ion channel types across the entire dendritic arbor. To achieve this, standard immunohistochemistry was combined with reconstruction and quantification procedures for the localization and relative distribution of ion channels with respect to dendritic morphology. This method can, in principle, be applied to any fluorescent signal, including fluorescently tagged membrane proteins, RNAs, or intracellular signaling molecules.
  Frontiers in Neural Circuits 04/2013; 7(61).
• Article: Functional architecture of the inferior colliculus revealed with voltage sensitive dyes

  Lakshmi Chandrasekaran, Ying Xiao, Shobhana Sivaramakrishnan
  [show abstract] [hide abstract]
  ABSTRACT: We used optical imaging with voltage-sensitive dyes to investigate the spatio-temporal dynamics of synaptically evoked activity in brain slices of the inferior colliculus (IC). Responses in transverse slices which preserve cross-frequency connections and in modified sagittal slices that preserve connections within frequency laminae were evoked by activating the lateral lemniscal tract. Comparing activity between small and large populations of cells revealed response areas in the central nucleus of the IC that were similar in magnitude but graded temporally. In transverse sections, these response areas are summed to generate a topographic response profile. Activity through the commissure to the contralateral IC required an excitation threshold that was reached when GABAergic inhibition was blocked. Within laminae, module interaction created temporal homeostasis. Diffuse activity evoked by a single lemniscal shock re-organized into distinct spatial and temporal compartments when stimulus trains were used, and generated a directional activity profile within the lamina. Using different stimulus patterns to activate subsets of microcircuits in the central nucleus of the IC, we found that localized responses evoked by low-frequency stimulus trains spread extensively when train frequency was increased, suggesting recruitment of silent microcircuits. Long stimulus trains activated a circuit specific to post-inhibitory rebound neurons. Rebound microcircuits were defined by a focal point of initiation that spread to an annular ring that oscillated between inhibition and excitation. We propose that much of the computing power of the IC is derived from local circuits, some of which are cell-type specific. These circuits organize activity within and across frequency laminae, and are critical in determining the stimulus-selectivity of auditory coding.
  Frontiers in Neural Circuits 03/2013;
• Article: Rat whisker motor cortex is subdivided into sensory-input and motor-output areas

  Jared B. Smith and Kevin D. Alloway
  [show abstract] [hide abstract]
  ABSTRACT: Rodent whisking is an exploratory behavior that can be modified by sensory feedback. Consistent with this, many whisker-sensitive cortical regions project to agranular motor (MI) cortex, but the relative topography of these afferent projections has not been established. Intracranial microstimulation (ICMS) evokes whisker movements that are used to map the functional organization of MI, but no study has compared the whisker-related inputs to MI with the ICMS sites that evoke whisker movements. To elucidate this relationship, anterograde tracers were placed in posterior parietal cortex (PPC) and in the primary (SI) and secondary (SII) somatosensory cortical areas so that their labeled projections to MI could be analyzed with respect to ICMS sites that evoke whisker movements. Projections from SI and SII terminate in a narrow zone that marks the transition between the medial (AGm) and lateral agranular (AGl) cortical areas, but PPC projects more medially and terminates in AGm proper. Paired recordings of MI neurons indicate that the region between AGm and AGl is highly responsive to whisker deflections, but neurons in AGm display negligible responses to whisker stimulation. By contrast, AGm microstimulation is more effective in evoking whisker movements than microstimulation of the transitional region between AGm and AGl. The AGm region was also found to contain a larger concentration of corticotectal neurons, which could convey whisker-related information to the facial nucleus. These results indicate that rat whisker motor cortex is comprised of at least two functionally distinct subregions: a sensory processing zone in the transitional region between AGm and AGl, and a motor output region located more medially in AGm proper.
  Frontiers in Neural Circuits 01/2013; 7:4.
• Article: CREB and neuronal selection for memory trace.

  Jieun Kim, Jeong-Tae Kwon, Hyung-Su Kim, Jin-Hee Han
  [show abstract] [hide abstract]
  ABSTRACT: Despite considerable progress over the past several decades, our understanding of the mechanisms underlying memory encoding, storage, and expression in a complex neural network are far from complete. In particular, how some neurons rather than others are selectively engaged to encode memory remains largely unknown. Using virus-mediated gene delivery into a small subset of neurons in a given network, molecular imaging of neuronal activity, pharmacological perturbation of specific neurons' activity and animal behavior assays, recent studies have begun to provide insight into molecular and cellular mechanisms responsible for the selection of neurons for inclusion into a memory trace. Here, we focus on a review of recent findings supporting the hypothesis that the level of the transcription factor CREB (cAMP/Ca(2+)-response element binding protein) is a key factor governing which neurons are recruited to a given memory trace. These recent findings open a new perspective on memory trace at the neural circuit level and also raise many important questions. Future studies employing more advanced neurobiological techniques for targeting defined populations of neurons and manipulating their activity in time and space in a complex neural network will give answers to these newly emerging questions and extend our understanding of the neurobiological basis of the memory trace.
  Frontiers in Neural Circuits 01/2013; 7:44.
• Article: Nanowire electrodes for high-density stimulation and measurement of neural circuits.

  Jacob T Robinson, Marsela Jorgolli, Hongkun Park
  [show abstract] [hide abstract]
  ABSTRACT: Brain-machine interfaces (BMIs) that can precisely monitor and control neural activity will likely require new hardware with improved resolution and specificity. New nanofabricated electrodes with feature sizes and densities comparable to neural circuits may lead to such improvements. In this perspective, we review the recent development of vertical nanowire (NW) electrodes that could provide highly parallel single-cell recording and stimulation for future BMIs. We compare the advantages of these devices and discuss some of the technical challenges that must be overcome for this technology to become a platform for next-generation closed-loop BMIs.
  Frontiers in Neural Circuits 01/2013; 7:38.
• Article: Regulation of zebrafish sleep and arousal states: current and prospective approaches.

  Cindy N Chiu, David A Prober
  [show abstract] [hide abstract]
  ABSTRACT: Every day, we shift among various states of sleep and arousal to meet the many demands of our bodies and environment. A central puzzle in neurobiology is how the brain controls these behavioral states, which are essential to an animal's well-being and survival. Mammalian models have predominated sleep and arousal research, although in the past decade, invertebrate models have made significant contributions to our understanding of the genetic underpinnings of behavioral states. More recently, the zebrafish has emerged as a promising model system for sleep and arousal research. Here we review experimental evidence that the zebrafish, a diurnal vertebrate, exhibits fundamental behavioral and neurochemical characteristics of mammalian sleep and arousal. We also propose how specific advantages of the zebrafish can be harnessed to advance the field. These include tractable genetics to identify and manipulate molecular and cellular regulators of behavioral states, optical transparency to facilitate in vivo observation of neural structure and function, and amenability to high-throughput drug screens to discover novel therapies for neurological disorders.
  Frontiers in Neural Circuits 01/2013; 7:58.
• Article: Monocular inhibition reveals temporal and spatial changes in gene expression in the primary visual cortex of marmoset.

  Yuki Nakagami, Akiya Watakabe, Tetsuo Yamamori
  [show abstract] [hide abstract]
  ABSTRACT: We investigated the time course of the expression of several activity-dependent genes evoked by visual inputs in the primary visual cortex (V1) in adult marmosets. In order to examine the rapid time course of activity-dependent gene expression, marmosets were first monocularly inactivated by tetrodotoxin (TTX), kept in darkness for two days, and then exposed to various length of light stimulation. Activity-dependent genes including HTR1B, HTR2A, whose activity-dependency were previously reported by us, and well-known immediate early genes (IEGs), c-FOS, ZIF268, and ARC, were examined by in situ hybridization. Using this system, first, we demonstrated the ocular dominance type of gene expression pattern in V1 under this condition. IEGs were expressed in columnar patterns throughout layers II-VI of all the tested monocular marmosets. Second, we showed the regulation of HTR1B and HTR2A expressions by retinal spontaneous activity, because HTR1B and HTR2A mRNA expressions sustained a certain level regardless of visual stimulation and were inhibited by a blockade of the retinal activity with TTX. Third, IEGs dynamically changed its laminar distribution from half an hour to several hours upon a stimulus onset with the unique time course for each gene. The expression patterns of these genes were different in neurons of each layer as well. These results suggest that the regulation of each neuron in the primary visual cortex of marmosets is subjected to different regulation upon the change of activities from retina. It should be related to a highly differentiated laminar structure of marmoset visual systems, reflecting the functions of the activity-dependent gene expression in marmoset V1.
  Frontiers in Neural Circuits 01/2013; 7:43.
• Article: Learning and exploration in action-perception loops.

  Daniel Y Little, Friedrich T Sommer
  [show abstract] [hide abstract]
  ABSTRACT: Discovering the structure underlying observed data is a recurring problem in machine learning with important applications in neuroscience. It is also a primary function of the brain. When data can be actively collected in the context of a closed action-perception loop, behavior becomes a critical determinant of learning efficiency. Psychologists studying exploration and curiosity in humans and animals have long argued that learning itself is a primary motivator of behavior. However, the theoretical basis of learning-driven behavior is not well understood. Previous computational studies of behavior have largely focused on the control problem of maximizing acquisition of rewards and have treated learning the structure of data as a secondary objective. Here, we study exploration in the absence of external reward feedback. Instead, we take the quality of an agent's learned internal model to be the primary objective. In a simple probabilistic framework, we derive a Bayesian estimate for the amount of information about the environment an agent can expect to receive by taking an action, a measure we term the predicted information gain (PIG). We develop exploration strategies that approximately maximize PIG. One strategy based on value-iteration consistently learns faster than previously developed reward-free exploration strategies across a diverse range of environments. Psychologists believe the evolutionary advantage of learning-driven exploration lies in the generalized utility of an accurate internal model. Consistent with this hypothesis, we demonstrate that agents which learn more efficiently during exploration are later better able to accomplish a range of goal-directed tasks. We will conclude by discussing how our work elucidates the explorative behaviors of animals and humans, its relationship to other computational models of behavior, and its potential application to experimental design, such as in closed-loop neurophysiology studies.
  Frontiers in Neural Circuits 01/2013; 7:37.
• Article: The motor cortex: a network tuned to 7-14 Hz.

  Manuel A Castro-Alamancos
  [show abstract] [hide abstract]
  ABSTRACT: The neocortex or six layer cortex consists of at least 52 cytoarchitectonically distinct areas in humans, and similar areas can be distinguished in rodents. Each of these areas has a defining set of extrinsic connections, identifiable functional roles, a distinct laminar arrangement, etc. Thus, neocortex is extensively subdivided into areas of anatomical and functional specialization, but less is known about the specialization of cellular and network physiology across areas. The motor cortex appears to have a distinct propensity to oscillate in the 7-14 Hz frequency range. Augmenting responses, normal mu and beta oscillations, and abnormal oscillations or after discharges caused by enhancing excitation or suppressing inhibition are all expressed around this frequency range. The substrate for this activity may be an excitatory network that is unique to the motor cortex or that is more strongly suppressed in other areas, such as somatosensory cortex. Interestingly, augmenting responses are dependent on behavioral state. They are abolished during behavioral arousal. Here, I briefly review this evidence.
  Frontiers in Neural Circuits 01/2013; 7:21.
• Article: Error detection and representation in the olivo-cerebellar system.

  Masao Ito
  [show abstract] [hide abstract]
  ABSTRACT: Complex spikes generated in a cerebellar Purkinje cell via a climbing fiber have been assumed to encode errors in the performance of neuronal circuits involving Purkinje cells. To reexamine this notion in this review, I analyzed structures of motor control systems involving the cerebellum. A dichotomy was found between the two types of error: sensory and motor errors play roles in the feedforward and feedback control conditions, respectively. To substantiate this dichotomy, here in this article I reviewed recent data on neuronal connections and signal contents of climbing fibers in the vestibuloocular reflex (VOR), optokinetic eye movement response, saccade, hand reaching, cursor tracking, as well as some other cases of motor control. In our studies, various sources of sensory and motor errors were located in the neuronal pathways leading to the inferior olive. We noted that during the course of evolution, control system structures involving the cerebellum changed rather radically from the prototype seen in the flocculonodular lobe and vermis to that applicable to the cerebellar hemisphere. Nevertheless, the dichotomy between sensory and motor errors is maintained.
  Frontiers in Neural Circuits 01/2013; 7:1.
• Article: Cortical output to fast and slow muscles of the ankle in the rhesus macaque.

  Heather M Hudson, Darcy M Griffin, Abderraouf Belhaj-Saïf, Paul D Cheney
  [show abstract] [hide abstract]
  ABSTRACT: The cortical control of fast and slow muscles of the ankle has been the subject of numerous reports yielding conflicting results. Although it is generally agreed that cortical stimulation yields short latency facilitation of fast muscles, the effects on the slow muscle, soleus, remain controversial. Some studies have shown predominant facilitation of soleus from the cortex while others have provided evidence of differential control in which soleus is predominantly inhibited from the cortex. The objective of this study was to investigate the cortical control of fast and slow muscles of the ankle using stimulus triggered averaging (StTA) of EMG activity, which is a sensitive method of detecting output effects on muscle activity. This method also has relatively high spatial resolution and can be applied in awake, behaving subjects. Two rhesus macaques were trained to perform a hindlimb push-pull task. Stimulus triggered averages (StTAs) of EMG activity (15, 30, and 60 μA at 15 Hz) were computed for four muscles of the ankle [tibialis anterior (TA), medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus] as the monkeys performed the task. Poststimulus facilitation (PStF) was observed in both the fast muscles (TA, MG, and LG) as well as the slow muscle (soleus) and was as common and as strong in soleus as in the fast muscles. However, while poststimulus suppression (PStS) was observed in all muscles, it was more common in the slow muscle compared to the fast muscles and was as common as facilitation at low stimulus intensities. Overall, our results demonstrate that cortical facilitation of soleus has an organization that is very similar to that of the fast ankle muscles. However, cortical inhibition is organized differently allowing for more prominent suppression of soleus motoneurons.
  Frontiers in Neural Circuits 01/2013; 7:33.
• Article: Neural circuits mediating olfactory-driven behavior in fish.

  Florence Kermen, Luis M Franco, Cameron Wyatt, Emre Yaksi
  [show abstract] [hide abstract]
  ABSTRACT: The fish olfactory system processes odor signals and mediates behaviors that are crucial for survival such as foraging, courtship, and alarm response. Although the upstream olfactory brain areas (olfactory epithelium and olfactory bulb) are well-studied, less is known about their target brain areas and the role they play in generating odor-driven behaviors. Here we review a broad range of literature on the anatomy, physiology, and behavioral output of the olfactory system and its target areas in a wide range of teleost fish. Additionally, we discuss how applying recent technological advancements to the zebrafish (Danio rerio) could help in understanding the function of these target areas. We hope to provide a framework for elucidating the neural circuit computations underlying the odor-driven behaviors in this small, transparent, and genetically amenable vertebrate.
  Frontiers in Neural Circuits 01/2013; 7:62.