scholarly journals A population of gap junction-coupled neurons drives recurrent network activity in a developing visual circuit

2016 ◽  
Vol 115 (3) ◽  
pp. 1477-1486 ◽  
Author(s):  
Zhenyu Liu ◽  
Christopher M. Ciarleglio ◽  
Ali S. Hamodi ◽  
Carlos D. Aizenman ◽  
Kara G. Pratt

In many regions of the vertebrate brain, microcircuits generate local recurrent activity that aids in the processing and encoding of incoming afferent inputs. Local recurrent activity can amplify, filter, and temporally and spatially parse out incoming input. Determining how these microcircuits function is of great interest because it provides glimpses into fundamental processes underlying brain computation. Within the Xenopus tadpole optic tectum, deep layer neurons display robust recurrent activity. Although the development and plasticity of this local recurrent activity has been well described, the underlying microcircuitry is not well understood. Here, using a whole brain preparation that allows for whole cell recording from neurons of the superficial tectal layers, we identified a physiologically distinct population of excitatory neurons that are gap junctionally coupled and through this coupling gate local recurrent network activity. Our findings provide a novel role for neuronal coupling among excitatory interneurons in the temporal processing of visual stimuli.

2001 ◽  
Vol 18 (3) ◽  
pp. 457-464 ◽  
Author(s):  
ZHENG LI ◽  
KATHERINE V. FITE

Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter in the vertebrate brain. It can exert its influence either as GABAergic projection pathways or as local interneurons, which play an essential role in many visual functions. However, no GABAergic visual pathways have been studied in frogs so far. In the present study, GABAergic pathways in the central visual system of Rana pipiens were investigated with double-labeling techniques, combining immunocytochemistry for GABA with Rhodamine microspheres for retrograde tracing. Three GABAergic visual pathways were identified: (1) a retino-tectal projection, from retina to the contralateral optic tectum (OT); (2) an ipsilateral projection from the nucleus of the basal optic root (nBOR) to the pretectal nucleus lentiformis mesencephali (nLM); and (3) a second-order pathway from the nucleus isthmi (NI), bilaterally, to the optic tectum. These results indicate that GABA is involved in both first-order (retina to optic tectum) as well as second-order (nucleus isthmi to optic tectum) visual projections in Rana pipiens, and may play a major role in mediating visuomotor reflexs such as optokinetic nystagmus or other visually guided behaviors.


2016 ◽  
Author(s):  
Alyssa M. Boasso ◽  
Hailey Mortimore ◽  
Rhonda Silva ◽  
Linh Aven ◽  
William J. Tyler

Achieving optimal human performance that involves cognitive or physical work requires quality sleep and a positive mental attitude. The ascending reticular activating system (RAS) represents a powerful set of endogenous neuromodulatory circuits that gate and tune global brain responses to internal and external cues, thereby regulating consciousness, alertness, and attention. The activity of two major RAS nuclei, the locus coeruleus (LC) and pedunculopontine nucleus (PPN), can be altered by trigeminal nerve modulation. Monosynaptic afferent inputs from the sensory components of trigeminal nerve branches project to the trigeminal sensory nuclear complex (TSNC), which has direct and polysynaptic connections to the LC and PPN. We previously found high-frequency (7 - 11 kHz) transdermal electrical neuromodulation (TEN) of the trigeminal nerve rapidly induces physiological relaxation, dampens sympathetic nervous system responses to acute stress, and suppresses levels of noradrenergic biomarkers. Given the established roles of LC and PPN neuronal activity in sleep regulation, psychophysiological arousal, and stress, we conducted three studies designed to test hypotheses that modulation of the TSNC can improve sleep quality and mood in healthy individuals (n = 99). Across a total of 1,386 days monitored, we observed TEN modulation of trigeminal and cervical nerves prior to sleep onset produced significant improvements in sleep quality and affective states, quantified using clinically validated surveys, overnight actigraph and heart rate recordings, and biochemical analyses compared to baseline or sham controls. Moreover, we observed some frequency dependence in that TEN delivered at lower frequencies (TENLF; 0.50 - 0.75 kHz) was significantly more effective at improving sleep quality and reducing anxiety than higher frequency TEN waveforms. Collectively our results indicate that transdermal electrical neuromodulation of trigeminal and cervical nerve branches can influence TSNC activity in a manner that significantly improves sleep quality and significantly reduces stress. We conclude that biasing RAS network activity to optimize sleep efficiency and enhance mood by electrically modulating TSNC activity through its afferent inputs holds tremendous potential for optimizing mental health and human performance.


2015 ◽  
Vol 113 (1) ◽  
pp. 400-407 ◽  
Author(s):  
Ali S. Hamodi ◽  
Kara G. Pratt

The Xenopus tadpole optic tectum is a multisensory processing center that receives direct visual input as well as nonvisual mechanosensory input. The tectal neurons that comprise the optic tectum are organized into layers. These neurons project their dendrites laterally into the neuropil where visual inputs target the distal region of the dendrite and nonvisual inputs target the proximal region of the same dendrite. The Xenopus tadpole tectum is a popular model to study the development of sensory circuits. However, whole cell patch-clamp electrophysiological studies of the tadpole tectum (using the whole brain or in vivo preparations) have focused solely on the deep-layer tectal neurons because only neurons of the deep layer are visible and accessible for whole cell electrophysiological recordings. As a result, whereas the development and plasticity of these deep-layer neurons has been well-studied, essentially nothing has been reported about the electrophysiology of neurons residing beyond this layer. Hence, there exists a large gap in our understanding about the functional development of the amphibian tectum as a whole. To remedy this, we developed a novel isolated brain preparation that allows visualizing and recording from all layers of the tectum. We refer to this preparation as the “horizontal brain slice preparation.” Here, we describe the preparation method and illustrate how it can be used to characterize the electrophysiology of neurons across all of the layers of the tectum as well as the spatial pattern of synaptic input from the different sensory modalities.


2020 ◽  
Author(s):  
Caitlin A. Murphy ◽  
Aeyal Raz ◽  
Matthew I. Banks

ABSTRACTAnesthetics influence consciousness in part via their actions on thalamocortical circuits. However, the extent to which volatile anesthetics affect distinct cellular and network components of these circuits remains unclear. Ex vivo brain slices provide a means by which investigators may probe discrete components of complex networks and disentangle potential mechanisms underlying the effects of volatile anesthetics on evoked responses. To isolate potential cell type- and pathway-specific drug effects in brain slices, investigators must be able to independently activate afferent fiber pathways, identify non-overlapping populations of cells, and apply volatile anesthetics to tissue in aqueous solution. In this protocol, we describe methods to measure optogenetically-evoked responses to two independent afferent pathways to neocortex in ex vivo brain slices. We record extracellular responses to assay network activity and conduct targeted whole-cell patch clamp recordings in somatostatin- and parvalbumin-positive interneurons. We also describe a means by which to deliver physiologically relevant concentrations of isoflurane via artificial cerebral spinal fluid to modulate cellular and network responses.SUMMARYEx vivo brain slices can be used to study the effects of volatile anesthetics on evoked responses to afferent inputs. We employ optogenetics to independently activate thalamocortical and corticocortical afferents to non-primary neocortex, and we modulate synaptic and network responses with isoflurane.


2016 ◽  
Author(s):  
Nikolay Chenkov ◽  
Henning Sprekeler ◽  
Richard Kempter

AbstractComplex patterns of neural activity appear during up-states in the neocortex and sharp waves in the hippocampus, including sequences that resemble those during prior behavioral experience. The mechanisms underlying this replay are not well understood. How can small synaptic footprints engraved by experience control large-scale network activity during memory retrieval and consolidation? We hypothesize that sparse and weak synaptic connectivity between Hebbian assemblies are boosted by pre-existing recurrent connectivity within them. To investigate this idea, we connect sequences of assemblies in randomly connected spiking neuronal networks with a balance of excitation and inhibition. Simulations and analytical calculations show that recurrent connections within assemblies allow for a fast amplification of signals that indeed reduces the required number of inter-assembly connections. Replay can be evoked by small sensory-like cues or emerge spontaneously by activity fluctuations. Global—potentially neuromodulatory—alterations of neuronal excitability can switch between network states that favor retrieval and consolidation.Author SummarySynaptic plasticity is the basis for learning and memory, and many experiments indicate that memories are imprinted in synaptic connections. However, basic mechanisms of how such memories are retrieved and consolidated remain unclear. In particular, how can one-shot learning of a sequence of events achieve a sufficiently strong synaptic footprint to retrieve or replay this sequence? Using both numerical simulations of spiking neural networks and an analytic approach, we provide a biologically plausible model for understanding how minute synaptic changes in a recurrent network can nevertheless be retrieved by small cues or even manifest themselves as activity patterns that emerge spontaneously. We show how the retrieval of exceedingly small changes in the connections across assemblies is robustly facilitated by recurrent connectivity within assemblies. This interaction between recurrent amplification within an assembly and the feed-forward propagation of activity across the network establishes a basis for the retrieval of memories.


2019 ◽  
Author(s):  
Tina Gothner ◽  
Pedro J. Gonçalves ◽  
Maneesh Sahani ◽  
Jennifer F. Linden ◽  
K. Jannis Hildebrandt

ABSTRACTSensory cortices must flexibly adapt their operations to internal states and external requirements. Modulation of specific inhibitory interneurons may provide a network-level mechanism for adjustments on behaviourally relevant timescales. Understanding of the computational roles of such modulation has mostly been restricted to phasic optogenetic activation and short, transient stimuli. Here, we aimed to extend the understanding of modulation of cortical inhibition by using sustained, network-wide optogenetic activation of parvalbumin-positive interneurons in core auditory cortex to study modulation of responses to transient, sustained, and naturalistic stimuli. We found highly conserved spectral and temporal tuning, despite profoundly reduced overall network activity. This reduction was predominantly divisive, and consistent across simple, complex, and naturalistic stimuli. A recurrent network model with power-law input-output functions replicated our results. We conclude that modulation of parvalbumin-positive interneurons on timescales typical of more sustained neuromodulation may provide a means for robust divisive gain control conserving stimulus representations.


2016 ◽  
Author(s):  
Rishidev Chaudhuri ◽  
Biyu He ◽  
Xiao-Jing Wang

The power spectrum of brain electric field potential recordings is dominated by an arrhythmic broadband signal but a mechanistic account of its underlying neural network dynamics is lacking. Here we show how the broadband power spectrum of field potential recordings can be explained by a simple random network of nodes near criticality. Such a recurrent network produces activity with a combination of a fast and a slow autocorrelation time constant, with the fast mode corresponding to local dynamics and the slow mode resulting from recurrent excitatory connections across the network. These modes are combined to produce a power spectrum similar to that observed in human intracranial EEG (i.e., electrocorticography, ECoG) recordings. Moreover, such a network naturally converts input correlations across nodes into temporal autocorrelation of the network activity. Consequently, increased independence between nodes results in a reduction in low-frequency power, which offers a possible explanation for observed changes in ECoG power spectra during task performance. Lastly, changes in network coupling produce changes in network activity power spectra reminiscent of those seen in human ECoG recordings across different arousal states. This model thus links macroscopic features of the empirical ECoG power spectrum to a parsimonious underlying network structure and proposes potential mechanisms for changes in ECoG power spectra observed across behavioral and arousal states. This provides a computational framework within which to generate and test hypotheses about the cellular and network mechanisms underlying whole brain electrical dynamics, their variations across behavioral states as well as abnormalities associated with brain diseases.


2020 ◽  
Author(s):  
Ashwin Vishwanathan ◽  
Alexandro D. Ramirez ◽  
Jingpeng Wu ◽  
Alex Sood ◽  
Runzhe Yang ◽  
...  

AbstractNeuronal wiring diagrams reconstructed from electron microscopic images are enabling new ways of attacking neuroscience questions. We address two central issues, modularity and neural coding, by reconstructing and analyzing a wiring diagram from a larval zebrafish brainstem. We identified a recurrently connected “center” within the 3000-node graph, and applied graph clustering algorithms to divide the center into two modules with stronger connectivity within than between modules. Outgoing connection patterns and registration to maps of neural activity suggested the modules were specialized for body and eye movements. The eye movement module further subdivided into two submodules corresponding to the control of the two eyes. We constructed a recurrent network model of the eye movement module with connection strengths estimated from synapse numbers. Neural activity in the model replicated the statistics of eye position encoding across multiple populations of neurons as observed by calcium imaging. Our findings show that synapse-level wiring diagrams can be used to extract structural modules with interpretable functions in the vertebrate brain, and can be related to the encoding of computational variables important for behavior. We also show through a potential synapse formalism that these modeling successes require true synaptic connectivity; connectivity inferred from arbor overlap is insufficient.


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