Excitatory Interactions Research Articles

Cortical Sensorimotor Reverberations

In this issue of Neuron, Manita et al. (2015) report that reciprocal excitatory interactions between higher-order frontal motor cortex and primary sensorimotor cortex might play a key role in hindlimb sensory perception in mice.

Colocalization of allatotropin and tachykinin-related peptides with classical transmitters in physiologically distinct subtypes of olfactory local interneurons in the cockroach (Periplaneta americana).

In the insect antennal lobe different types of local interneurons mediate complex excitatory and inhibitory interactions between the glomerular pathways to structure the spatiotemporal representation of odors. Mass spectrometric and immunohistochemical studies have shown that in local interneurons classical neurotransmitters are likely to colocalize with a variety of substances that can potentially act as cotransmitters or neuromodulators. In the antennal lobe of the cockroach Periplaneta americana, gamma-aminobutyric acid (GABA) has been identified as the potential inhibitory transmitter of spiking type I local interneurons, whereas acetylcholine is most likely the excitatory transmitter of nonspiking type IIa1 local interneurons. This study used whole-cell patch clamp recordings combined with single-cell labeling and immunohistochemistry to test if the GABAergic type I local interneurons and the cholinergic type IIa1 local interneurons express allatotropin and tachykinin-related neuropeptides (TKRPs). These are two of the most abundant types of peptides in the insect antennal lobe. GABA-like and choline acetyltransferase (ChAT)-like immunoreactivity were used as markers for GABAergic and cholinergic neurons, respectively. About 50% of the GABA-like immunoreactive (-lir) spiking type I local interneurons were allatotropin-lir, and ∼ 40% of these neurons were TKRP-lir. About 20% of nonspiking ChAT-lir type IIa1 local interneurons were TKRP-lir. Our results suggest that in subpopulations of GABAergic and cholinergic local interneurons, allatotropin and TKRPs might act as cotransmitters or neuromodulators. To unequivocally assign neurotransmitters, cotransmitters, and neuromodulators to identified classes of antennal lobe neurons is an important step to deepen our understanding of information processing in the insect olfactory system.

Midline section of the medulla abolishes inspiratory activity and desynchronizes pre-inspiratory neuron rhythm on both sides of the medulla in newborn rats.

Each half of the medulla contains respiratory neurons that constitute two generators that control respiratory rhythm. One generator consists of the inspiratory neurons in the pre-Bötzinger complex (preBötC); the other, the pre-inspiratory (Pre-I) neurons in the parafacial respiratory group (pFRG), rostral to the preBötC. We investigated the contribution of the commissural fibers, connecting the respiratory rhythm generators located on the opposite side of the medulla to the generation of respiratory activity in brain stem-spinal cord preparation from 0- to 1-day-old rats. Pre-I neuron activity and the facial nerve and/or first lumbar (L1) root activity were recorded as indicators of the pFRG-driven rhythm. Fourth cervical ventral root (C4) root and/or hypoglossal (XII) nerve activity were recorded as indicators of preBötC-driven inspiratory activity. We found that a midline section that interrupted crossed fibers rostral to the obex irreversibly eliminated C4 and XII root activity, whereas the Pre-I neurons, facial nerve, and L1 roots remained rhythmically active. The facial and contralateral L1 nerve activities were synchronous, whereas right and left facial (and right and left L1) nerves lost synchrony. Optical recordings demonstrated that pFRG-driven burst activity was preserved after a midline section, whereas the preBötC neurons were no longer rhythmic. We conclude that in newborn rats, crossed excitatory interactions (via commissural fibers) are necessary for the generation of inspiratory bursts but not for the generation of rhythmic Pre-I neuron activity.

Excitatory and inhibitory projections in parallel pathways from the inferior colliculus to the auditory thalamus.

Individual subdivisions of the medial geniculate body (MG) receive a majority of their ascending inputs from 1 or 2 subdivisions of the inferior colliculus (IC). This establishes parallel pathways that provide a model for understanding auditory projections from the IC through the MG and on to auditory cortex. A striking discovery about the tectothalamic circuit was identification of a substantial GABAergic component. Whether GABAergic projections match the parallel pathway organization has not been examined. We asked whether the parallel pathway concept is reflected in guinea pig tectothalamic pathways and to what degree GABAergic cells contribute to each pathway. We deposited retrograde tracers into individual MG subdivisions (ventral, MGv; medial, MGm; dorsal, MGd; suprageniculate, MGsg) to label tectothalamic cells and used immunochemistry to identify GABAergic cells. The MGv receives most of its IC input (~75%) from the IC central nucleus (ICc); MGd and MGsg receive most of their input (~70%) from IC dorsal cortex (ICd); and MGm receives substantial input from both ICc (~40%) and IC lateral cortex (~40%). Each MG subdivision receives additional input (up to 32%) from non-dominant IC subdivisions, suggesting cross-talk between the pathways. The proportion of GABAergic cells in each pathway depended on the MG subdivision. GABAergic cells formed ~20% of IC inputs to MGv or MGm, ~11% of inputs to MGd, and 4% of inputs to MGsg. Thus, non-GABAergic (i.e., glutamatergic) cells are most numerous in each pathway with GABAergic cells contributing to different extents. Despite smaller numbers of GABAergic cells, their distributions across IC subdivisions mimicked the parallel pathways. Projections outside the dominant pathways suggest opportunities for excitatory and inhibitory crosstalk. The results demonstrate parallel tectothalamic pathways in guinea pigs and suggest numerous opportunities for excitatory and inhibitory interactions within and between pathways.

An Unconventional Glutamatergic Circuit in the Retina Formed by vGluT3 Amacrine Cells

In the vertebrate retina, glutamate is traditionally thought to be released only by photoreceptors and bipolar cells to transmit visual signals radially along parallel ON and OFF channels. Lateral interactions in the inner retina are mediated by amacrine cells, which are thought to be inhibitory neurons. Here, we report calcium-dependent glutamate release from vGluT3-expressing amacrine cells (GACs) in the mouse retina. GACs provide an excitatory glutamatergic input to ON-OFF and ON direction-selective ganglion cells (DSGCs) and a subpopulation of W3 ganglion cells, but not to starburst amacrine cells. GACs receive excitatory inputs from both ON and OFF channels, generate ON-OFF light responses with a medium-center, wide-surround receptive field structure, and directly regulate ganglion cell activity. The results reveal a functional glutamatergic circuit that mediates noncanonical excitatory interactions in the retina and probably plays a role in generating ON-OFF responses, crossover excitation, and lateral excitation.

Endogenous cholinergic input to the pontine REM sleep generator is not required for REM sleep to occur.

Initial theories of rapid eye movement (REM) sleep generation posited that induction of the state required activation of the pontine subceruleus (SubC) by cholinergic inputs. Although the capacity of cholinergic neurotransmission to contribute to REM sleep generation has been established, the role of cholinergic inputs in the generation of REM sleep is ultimately undetermined as the critical test of this hypothesis (local blockade of SubC acetylcholine receptors) has not been rigorously performed. We used bilateral microdialysis in freely behaving rats (n = 32), instrumented for electroencephalographic and electromyographic recording, to locally manipulate neurotransmission in the SubC with select drugs. As predicted, combined microperfusion of D-AP5 (glutamate receptor antagonist) and muscimol (GABAA receptor agonist) in the SubC virtually eliminated REM sleep. However, REM sleep was not reduced by scopolamine microperfusion in this same region, at a concentration capable of blocking the effects of cholinergic receptor stimulation. This result suggests that transmission of REM sleep drive to the SubC is acetylcholine-independent. Although SubC cholinergic inputs are not majorly involved in REM sleep generation, they may perform a minor function in the reinforcement of transitions into REM sleep, as evidenced by increases in non-REM-to-REM sleep transition duration and failure rate during cholinergic receptor blockade. Cholinergic receptor antagonism also attenuated the normal increase in hippocampal θ oscillations that characterize REM sleep. Using computational modeling, we show that our in vivo results are consistent with a mutually excitatory interaction between the SubC and cholinergic neurons where, importantly, cholinergic neuron activation is gated by SubC activity.

Cellular mechanisms generating bursting activity in neuronal networks

An open question in neuroscience is how the temporal characteristics of bursting activity are controlled by intrinsic biophysical characteristics. We present two mechanisms organized around the cornerstone bifurcation in a 3D Hodgkin-Huxley style neuronal model. This bifurcation satisfies the criteria for both the Shilnikov blue sky catastrophe and the saddle-node bifurcation on an invariant circle (SNIC) [1-3]. The burst duration (BD) and interburst interval (IBI) increase as the inverse of the square root of the difference between the corresponding parameter and its bifurcation value. The cornerstone bifurcation also determines the stereotypical transient responses of silent and spiking neurons [3]. The mechanisms presented here are based on these transient responses. The first mechanism described half-center oscillator consisting of two intrinsically silent, mutually inhibitory neurons (Figure 1AB). These two neurons were in the silent parameter regime but close to the cornerstone bifurcation. The two coupled neurons showed anti-phase bursting activity without the release and escape mechanisms. We found that if the half-activation voltage of a non-inactivating potassium current (V1/2,mk2) was systematically shifted towards the bifurcation value for the saddle-node bifurcation of periodic orbits, the BDs of both neurons increased in accordance with the inverse-square-root law and exhibited linear dependence on the spike number per burst. Figure 1 The cornerstone bifurcation generates mechanisms controlling bursting in neural networks. (A). Two endogenously silent, mutually inhibitory coupled neurons produce alternating bursting activity. V1/2,mk2 controls BDs. (B). The BDs are depicted as blue ... The second mechanism described the bursting activity of two intrinsically spiking, mutually excitatory neurons. The parameters of the neurons were in vicinity of the cornerstone bifurcation. This network exhibited synchronized bursting (Figure 1CD). Remarkably, excitatory interaction between endogenously spiking neurons essentially led to reduction of excitability of the network. When the half-activation voltage of hyperpolarization-activated current (V1/2,mh) was systematically shifted to the bifurcation value, IBIs of both neurons increased in accordance with the inverse-square-root law and the BDs and the number of spikes per burst stayed constant (6 spikes per burst). This study reveals new mechanisms controlling bursting activity in small neuronal networks based on cellular properties determining transient responses of endogenously spiking and silent neurons. These mechanisms are generic and could govern the bursting regimes in rhythmic neuronal network such as central pattern generators.

Dynamics of dichoptic masking in the primary visual cortex

The inputs from the two eyes interact in a nonlinear fashion. This interaction can be either excitatory or inhibitory: Excitatory interaction (combination) occurs first in the primary visual cortex but little is known about the site of the inhibitory interaction (suppression). To investigate the latter, experimental paradigms typically present distinct inputs to the eyes (dichoptic presentation, one target and one mask are respectively presented to different eyes at the same time). Here we used magnetoencephalography (MEG) source imaging to establish the site of the cortical neural signature of interocular suppression in visual cortex. We presented different noise stimuli to each eye: The target-noise was presented for contrasts ranging between 0 and 32 %. The mask-contrast was presented to the other eye at fixed contrast (32%). We flickered the two noise stimuli (4 and 6 Hz) to elicit a frequency-tagged steady-state visual evoked response (SSVER) that was readily detectable in MEG traces [1]. Four participants passively observed the visual presentation while keeping their gaze fixed on the center of the screen. The Brainstorm application was used to analyze the MEG data [3]. MEG source time series were extracted from cortical regions of interest (ROIs) defined from the visual retinotopic maps of each participant obtained from previous fMRI acquisitions. Using the power of the cortical responses to the frequency-tagged stimuli, we constructed contrast response functions for all the ROIs (Figure 1 A). To investigate dynamics of propagation of the response along visual cortical areas, the instantaneous phase of the signal was identified in each ROI. As expected [2], when the target was presented alone, the power of the responses was found to increase monotonically with contrast (Figure 1 B, solid line). When a mask was added to the other eye, the contrast response was attenuated (Figure 1 B, dotted line). Interestingly, the mask presented at a fixed contrast was also found to be gradually suppressed with increasing target contrast (Figure 1 C). These effects were revealed for responses as early as the primary visual cortex. In the time-domain, we detected a progressive phase shift between the cortical responses along the ventral and dorsal streams. Figure 1 A. Localization of V1 on the activity map B. Normalized power of SSVER response as a function of contrast for target only (solid line), target and mask (dotted line); C. Normalized power in a 32% contrast mask as the contrast in the target is increasing. ...

Network Activity of Neurons in the Frontal and Motor Areas of the Cortex in Cats in Situations of Simple and Complex Decision Taking

The organization of the network activity of neurons in the frontal and motor areas of the cortex was demonstrated in cats taking simple (no choice) and complex decisions with the opportunity to choose a behavioral strategy. On acquisition of delayed reflexes with a single reinforcement (no choice), there were no behavioral differences between the animals and a high level of performance of correct responses. In a complex situation, with the “right” to choose food reinforcements of different values, the same animals differed in their behavioral strategies and showed different levels of ability to solve the task. Assessment of neuron network activity revealed differences in the organization of cell ensembles in the frontal and motor areas of the cortex in situations of taking simple and complex decisions. In the complex decision situation, the motor cortex showed a decrease in the number of excitatory interneuronal interactions, suggesting organization of inhibitory circuits in the local networks. In the frontal cortex in the same situation, the network activity of cells remained unaltered and the only change was a tendency to an increase in this parameter in erroneous responses.

Human urothelial cell lines as potential models for studying cannabinoid and excitatory receptor interactions in the urinary bladder

To characterize human urothelial cell lines' cannabinoid receptor expression and evaluate their possible use for studying signalling interactions with purinergic and muscarinic receptor activation. PCR was used to detect cannabinoid (CB), muscarinic and purinergic receptor transcripts in HCV29 and UROtsa cells, whilst immunofluorescence evaluated protein expression and localization of cannabinoid receptors. The effect of CB1 agonist (ACEA) on carbachol- and ATP-induced changes in intracellular calcium ([Ca(2+)]i) levels was measured using fluorimetry. The ability of ACEA to reduce intracellular cAMP was investigated in HCV29 cells. CB1 and GPR55 receptor transcripts were detected in HCV29 and UROtsa cells, respectively. Immunofluorescence showed positive staining for CB1 in the HCV29 cells. Both cell lines expressed transcript levels for muscarinic receptors, but carbachol did not raise [Ca(2+)]i levels indicating a lack or low expression of G(q)-coupled muscarinic receptors. Transcripts for purinergic receptors were detected; ATP significantly increased [Ca(2+)]i in HCV29 and UROtsa cells by 395 ± 61 and 705 ± 100 nM (mean ± SEM, n = 6), respectively. ACEA did not alter ATP-induced [Ca(2+)]i or cAMP levels in HCV29 cells. Whilst HCV29 cells expressed CB1 and UROtsa cells expressed GPR55 receptors, these were not functionally coupled to the existing purinergic-driven increase in Ca2+ as such they do not represent a good model to study signalling interactions.

A novel dynamic modeling approach for predicting building energy performance

This paper presents a new methodology for modeling building energy performance that addresses some important limitations of building simulation. This new methodology develops a physical model for accurately predicting indoor environmental conditions and energy consumption by selecting best match parameters and variables. The innovative aspect of the proposed methodology is the introduction of open and closed loop system approaches to dynamically model the complex interaction of factors that contribute to building thermal performance and their uncertainties. This allows simultaneous tracking of both the lead and lag times between heating excitations and indoor thermal responses to account for their mutually excitatory interaction. The model system is solved using a Laplace transform technique, with an explicit solution that includes physical and generalized parameters calibrated by measurements. Singular value decomposition techniques are applied to further determine the model variables for the best approximation using lower dimensions. As a result the model complexity and the model parameters and variables are minimized while still preserving the physical meaning of the model. A careful, detailed validation and assessment of the model performance is conducted using a case study of a dance hall at a swim center (R2>0.9). A further validation of the model is also undertaken by assessing its forecasting capability against benchmark persistence models. The proposed model outperforms the benchmarks especially over longer time horizons. The methodology is useful in developing a minimal but comprehensive and accurate energy performance physical model which can reliably capture the dynamics of building thermal and energy performance. The proposed method can serve the needs of prediction and control applications in a wide variety of building types and can be incorporated into the most commonly used simulation models.

Choline acetyltransferase‐like immunoreactivity in a physiologically distinct subtype of olfactory nonspiking local interneurons in the cockroach (periplaneta americana)

Behavioral and physiological studies have shown that local interneurons are pivotal for processing odor information in the insect antennal lobe. They mediate inhibitory and excitatory interactions between the glomerular pathways and ultimately shape the tuning profile of projection neurons. To identify putative cholinergic local interneurons in the antennal lobe of Periplaneta americana, an antibody raised against the biosynthetic enzyme choline acetyltransferase (ChAT) was applied to individual morphologically and electrophysiologically characterized local interneurons. In nonspiking type IIa1 local interneurons, which were classified in this study, we found ChAT-like immunoreactivity suggesting that they are most likely excitatory. This is a well-defined population of neurons that generates Ca(2+) -driven spikelets upon depolarization and stimulation with odorants, but not Na(+) -driven action potentials, because they lack voltage-activated transient Na(+) currents. The nonspiking type IIa2 and type IIb local interneurons, in which Ca(2+) -driven spikelets were absent, had no ChAT-like immunoreactivity. The GABA-like immunoreactive, spiking type I local interneurons had no ChAT-like immunoreactivity. In addition, we showed that uniglomerular projection neurons with cell bodies located in the ventral portion of the ventrolateral somata group and projections along the inner antennocerebral tract exhibited ChAT-like immunoreactivity. Assigning potential transmitters and neuromodulators to distinct morphological and electrophysiological types of antennal lobe neurons is an important prerequisite for a detailed understanding of odor information processing in insects.

Computational modeling of spinal neural circuits involved in transition to hopping pattern in EphA4 knock-out mice

According to resent studies [1,3] the spinal cord neural circuits involved in left-right coordination of locomotor activity include (a) excitatory and inhibitory commissural interneurons (CINs) with axons crossing the midline and (b) excitatory (glutamatergic) interneurons with ipsilateral axon projections activating CIN pathways. The distribution and guidance of axonal projections of the glumatergic neurons during development critically depend on the EphA4 receptors, so that in EphA4 knock-out (KO) mice the normal left-right alternating pattern of walking is replaced with a hopping gait [3]. Isolated spinal cord preparations from EphA4 KO mice also exhibit a synchronized left and right locomotor activity [3]. The pharmacological enforcement of inhibition recovers the normal left-right alternating locomotor pattern in these preparations [3]. It was suggested [2] that switching to a left-right synchronized hoping pattern in the EphA4 KO mice might result from an abnormal midline crossing of axons of glutamatergic neurons that are normally distributed ipsilaterally. This suggestion has been directly confirmed in anatomical studies [4]. To further evaluate this idea we developed a computational model of neural circuitries in the spinal cord with left and right rhythm generators (RGs) containing sub-populations of EphA4-positive excitatory neurons projecting to the populations of CINs responsible for left-right alternation (see Figure ​Figure1).1). The model includes interacting populations of spinal interneurons modeled in the Hodgkin-Huxley style. To simulate changes in the EphA4 KO spinal circuits, the axons of the EphA4-positive neurons were redistributed and partly redirected to the contralateral side. As a result, the excitatory interactions between left and right RGs overcame their inhibitory interactions hence synchronizing their activity resulting in a hopping-like output pattern. A subsequent increase of inhibition in the model could recover the normal left-right alternating pattern. The model proposes a mechanistic explanation for the hopping gait in EphA4 KO mice and provides insights into the organization of the locomotor central pattern generator. Figure 1 Schematic of spinal circuits in the model for a normal (A) and EphA4 KO (B)

Binocular activation elicits differences in neurometabolic coupling in visual cortex

Non-invasive brain imaging requires comprehensive interpretation of hemodynamic signals. In functional magnetic resonance imaging, blood oxygen level dependent (BOLD) signals are used to infer neural processes. This necessitates a clear understanding of how BOLD signals and neural activity are related. One fundamental question concerns the relative importance of synaptic activity and spiking discharge. Although these two components are related, most previous work shows that synaptic activity is better reflected in the BOLD signal. However, the mechanisms of this relationship are not clear. The BOLD signal depends on relative changes in cerebral blood flow and cerebral metabolic rate of oxygen. Oxygen metabolism changes are difficult to measure with current imaging techniques, but it is possible to obtain direct quantitative simultaneous in vivo measurement of tissue oxygen and co-localized underlying neural activity. Here, we use this approach with a specific binocular stimulus protocol in order to activate inhibitory and excitatory neuronal pathways in the visual cortex. During excitatory binocular interaction, we find that metabolic, spiking, and local field potential responses are correlated. However, during suppressive binocular interaction, spiking activity and local field potentials (LFP) are dissociated while only the latter is coupled with metabolic response. These results suggest that inhibitory connections may be a key factor in the dissociation between LFP and spiking activity, which may contribute substantially to the close coupling between the BOLD signal and synchronized synaptic activity in the brain.

Extensive excitatory network interactions shape temporal processing of communication signals in a model sensory system

Many sensory brain regions are characterized by extensive local network interactions. However, we know relatively little about the contribution of this microcircuitry to sensory coding. Detailed analyses of neuronal microcircuitry are usually performed in vitro, whereas sensory processing is typically studied by recording from individual neurons in vivo. The electrosensory pathway of mormyrid fish provides a unique opportunity to link in vitro studies of synaptic physiology with in vivo studies of sensory processing. These fish communicate by actively varying the intervals between pulses of electricity. Within the midbrain posterior exterolateral nucleus (ELp), the temporal filtering of afferent spike trains establishes interval tuning by single neurons. We characterized pairwise neuronal connectivity among ELp neurons with dual whole cell recording in an in vitro whole brain preparation. We found a densely connected network in which single neurons influenced the responses of other neurons throughout the network. Similarly tuned neurons were more likely to share an excitatory synaptic connection than differently tuned neurons, and synaptic connections between similarly tuned neurons were stronger than connections between differently tuned neurons. We propose a general model for excitatory network interactions in which strong excitatory connections both reinforce and adjust tuning and weak excitatory connections make smaller modifications to tuning. The diversity of interval tuning observed among this population of neurons can be explained, in part, by each individual neuron receiving a different complement of local excitatory inputs.

Structure of Spike Count Correlations Reveals Functional Interactions between Neurons in Dorsolateral Prefrontal Cortex Area 8a of Behaving Primates

Neurons within the primate dorsolateral prefrontal cortex (dlPFC) are clustered in microcolumns according to their visuospatial tuning. One issue that remains poorly investigated is how this anatomical arrangement influences functional interactions between neurons during behavior. To investigate this question we implanted 4 mm×4 mm multielectrode arrays in two macaques' dlPFC area 8a and measured spike count correlations (rsc) between responses of simultaneously recorded neurons when animals maintained stationary gaze. Positive and negative rsc were significantly higher than predicted by chance across a wide range of inter-neuron distances (from 0.4 to 4 mm). Positive rsc were stronger between neurons with receptive fields (RFs) separated by ≤90° of angular distance and progressively decreased as a function of inter-neuron physical distance. Negative rsc were stronger between neurons with RFs separated by >90° and increased as a function of inter-neuron distance. Our results show that short- and long-range functional interactions between dlPFC neurons depend on the physical distance between them and the relationship between their visuospatial tuning preferences. Neurons with similar visuospatial tuning show positive rsc that decay with inter-neuron distance, suggestive of excitatory interactions within and between adjacent microcolumns. Neurons with dissimilar tuning from spatially segregated microcolumns show negative rsc that increase with inter-neuron distance, suggestive of inhibitory interactions. This pattern of results shows that functional interactions between prefrontal neurons closely follow the pattern of connectivity reported in anatomical studies. Such interactions may be important for the role of the prefrontal cortex in the allocation of attention to targets in the presence of competing distracters.

I think ICAN: modulation of TRPM4 channels may contribute not only to the emergence of rhythm, but robust output and metabolic sensitivity of the preBötzinger Complex inspiratory network

Understanding the mechanisms by which central rhythm generators (CRGs) produce the neural rhythms that drive behaviours such as locomotion, chewing and breathing is a longstanding, fundamental problem that also has great clinical relevance. A topic of current debate is whether the basis of CRG function resides in the intrinsic auto-rhythmic properties of pacemaker neurons or emergent properties of the network (Del Negro & Hayes, 2008). Strong support for the latter comes from work in the preBotzinger complex (preBotC, a region critical for rhythm generation) of the inspiratory network that shows powerful functional links among AMPA receptors, Ca2+ channels, group I metabotropic glutamate receptors (mGluRs) and the TRPM4-mediated (transient receptor potential melastatin 4 subtype), burst-generating, non-specific cation current, ICAN (Mironov 2008; Pace & Del Negro, 2008). In this model, referred to as the group pacemaker hypothesis, synaptically released glutamate periodically activates AMPA and group I mGluRs. AMPA receptor-mediated depolarization evokes Ca2+ current via voltage-gated Ca2+ channels. Inositol 1,4,5-trisphosphate (IP3) receptors bind this Ca2+ as well as IP3 synthesized as a result of mGluR activation to cause regenerative intracellular Ca2+ release. Ca2+ from Ca2+ channels and intracellular stores evokes ICAN, which provides the bulk of the inward current underlying the inspiratory drive potential. Thus, the mechanism of rhythm generation in vitro emerges from the properties of a network in which latent burst-generating, intrinsic conductances are recruited by excitatory synaptic interactions among preBotC inspiratory neurons (Feldman & Del Negro, 2006; Pace & Del Negro, 2008).

Modelling Dyadic Interaction with Hawkes Processes

We apply the Hawkes process to the analysis of dyadic interaction. The Hawkes process is applicable to excitatory interactions, wherein the actions of each individual increase the probability of further actions in the near future. We consider the representation of the Hawkes process both as a conditional intensity function and as a cluster Poisson process. The former treats the probability of an action in continuous time via non-stationary distributions with arbitrarily long historical dependency, while the latter is conducive to maximum likelihood estimation using the EM algorithm. We first outline the interpretation of the Hawkes process in the dyadic context, and then illustrate its application with an example concerning email transactions in the work place.

Synchronization and desynchronization in epilepsy: controversies and hypotheses

Epilepsy has been historically seen as a functional brain disorder associated with excessive synchronization of large neuronal populations leading to a hypersynchronous state. Recent evidence showed that epileptiform phenomena, particularly seizures, result from complex interactions between neuronal networks characterized by heterogeneity of neuronal firing and dynamical evolution of synchronization. Desynchronization is often observed preceding seizures or during their early stages; in contrast, high levels of synchronization observed towards the end of seizures may facilitate termination. In this review we discuss cellular and network mechanisms responsible for such complex changes in synchronization. Recent work has identified cell-type-specific inhibitory and excitatory interactions, the dichotomy between neuronal firing and the non-local measurement of local field potentials distant to that firing, and the reflection of the neuronal dark matter problem in non-firing neurons active in seizures. These recent advances have challenged long-established views and are leading to a more rigorous and realistic understanding of the pathophysiology of epilepsy.

Physiology and Plasticity of Interhemispheric Connections

Physiology and Plasticity of Interhemispheric Connections