State-dependent Modulation Research Articles

Covariation of pupillary and auditory cortical activity in rats under isoflurane anesthesia

Very slow fluctuations of spontaneous activities significantly influence not only behavioral performance in a conscious state, but also neural activities in an unconscious state. Covariation of pupil and cortical activities may lend important insights into the state-dependent modulation of stimulus encoding, yet this phenomenon has received little attention, especially with regard to non-visual cortices. In the present study, we investigated co-fluctuation of pupil size and neural activity in the auditory cortex of rats under isoflurane anesthesia. Pupil fluctuation consisted of longitudinal irregular shifts, and 1-min cyclic modulations. Both spontaneous and auditory-evoked potentials (AEPs) covaried with the longitudinal fluctuation of pupil size, but not with the 1-min cycle. Pupil size exhibited a positive correlation with spontaneous activity and negative correlation with AEP amplitude, particularly when the pupil size was beyond the normal range. Stimulus-specific adaptation characterized using an oddball paradigm was less dependent on pupil size than AEP. In contrast to the cortical activity, heart rate covaried with pupil size with the 1-min oscillatory component, but not the non-oscillatory component. Furthermore, light exposure induced the pupil reflex through the autonomic system, but did not modify cortical activity, indicating that autonomic activity was not causing the cortical modulation. These results together suggest that cortical activities spontaneously covary with pupillary activity through central cholinergic modulation that triggers sympathetic nerve activation. Such a state-dependent property may be a confounding factor in cortical electrophysiology studies.

Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output.

SummaryNeuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed) firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1) a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior.

Dynamic synchronization of ongoing neuronal activity across spinal segments regulates sensory information flow.

Previous studies on the correlation between spontaneous cord dorsum potentials recorded in the lumbar spinal segments of anaesthetized cats suggested the operation of a population of dorsal horn neurones that modulates, in a differential manner, transmission along pathways mediating Ib non-reciprocal postsynaptic inhibition and pathways mediating primary afferent depolarization and presynaptic inhibition. In order to gain further insight into the possible neuronal mechanisms that underlie this process, we have measured changes in the correlation between the spontaneous activity of individual dorsal horn neurones and the cord dorsum potentials associated with intermittent activation of these inhibitory pathways. We found that high levels of neuronal synchronization within the dorsal horn are associated with states of incremented activity along the pathways mediating presynaptic inhibition relative to pathways mediating Ib postsynaptic inhibition. It is suggested that ongoing changes in the patterns of functional connectivity within a distributed ensemble of dorsal horn neurones play a relevant role in the state-dependent modulation of impulse transmission along inhibitory pathways, among them those involved in the central control of sensory information. This feature would allow the same neuronal network to be involved in different functional tasks.

A neural population model incorporating dopaminergic neurotransmission during complex voluntary behaviors.

Assessing brain activity during complex voluntary motor behaviors that require the recruitment of multiple neural sites is a field of active research. Our current knowledge is primarily based on human brain imaging studies that have clear limitations in terms of temporal and spatial resolution. We developed a physiologically informed non-linear multi-compartment stochastic neural model to simulate functional brain activity coupled with neurotransmitter release during complex voluntary behavior, such as speech production. Due to its state-dependent modulation of neural firing, dopaminergic neurotransmission plays a key role in the organization of functional brain circuits controlling speech and language and thus has been incorporated in our neural population model. A rigorous mathematical proof establishing existence and uniqueness of solutions to the proposed model as well as a computationally efficient strategy to numerically approximate these solutions are presented. Simulated brain activity during the resting state and sentence production was analyzed using functional network connectivity, and graph theoretical techniques were employed to highlight differences between the two conditions. We demonstrate that our model successfully reproduces characteristic changes seen in empirical data between the resting state and speech production, and dopaminergic neurotransmission evokes pronounced changes in modeled functional connectivity by acting on the underlying biological stochastic neural model. Specifically, model and data networks in both speech and rest conditions share task-specific network features: both the simulated and empirical functional connectivity networks show an increase in nodal influence and segregation in speech over the resting state. These commonalities confirm that dopamine is a key neuromodulator of the functional connectome of speech control. Based on reproducible characteristic aspects of empirical data, we suggest a number of extensions of the proposed methodology building upon the current model.

Functional imaging of cortical feedback projections to the olfactory bulb.

Processing of sensory information is substantially shaped by centrifugal, or feedback, projections from higher cortical areas, yet the functional properties of these projections are poorly characterized. Here, we used genetically-encoded calcium sensors (GCaMPs) to functionally image activation of centrifugal projections targeting the olfactory bulb (OB). The OB receives massive centrifugal input from cortical areas but there has been as yet no characterization of their activity in vivo. We focused on projections to the OB from the anterior olfactory nucleus (AON), a major source of cortical feedback to the OB. We expressed GCaMP selectively in AON projection neurons using a mouse line expressing Cre recombinase (Cre) in these neurons and Cre-dependent viral vectors injected into AON, allowing us to image GCaMP fluorescence signals from their axon terminals in the OB. Electrical stimulation of AON evoked large fluorescence signals that could be imaged from the dorsal OB surface in vivo. Surprisingly, odorants also evoked large signals that were transient and coupled to odorant inhalation both in the anesthetized and awake mouse, suggesting that feedback from AON to the OB is rapid and robust across different brain states. The strength of AON feedback signals increased during wakefulness, suggesting a state-dependent modulation of cortical feedback to the OB. Two-photon GCaMP imaging revealed that different odorants activated different subsets of centrifugal AON axons and could elicit both excitation and suppression in different axons, indicating a surprising richness in the representation of odor information by cortical feedback to the OB. Finally, we found that activating neuromodulatory centers such as basal forebrain drove AON inputs to the OB independent of odorant stimulation. Our results point to the AON as a multifunctional cortical area that provides ongoing feedback to the OB and also serves as a descending relay for other neuromodulatory systems.

Odor- and state-dependent olfactory tubercle local field potential dynamics in awake rats

The olfactory tubercle (OT), a trilaminar structure located in the basal forebrain of mammals, is thought to play an important role in olfaction. While evidence has accumulated regarding the contributions of the OT to odor information processing, studies exploring the role of the OT in olfaction in awake animals remain unavailable. In the present study, we begin to address this void through multiday recordings of local field potential (LFP) activity within the OT of awake, freely exploring Long-Evans rats. We observed spontaneous OT LFP activity consisting of theta- (2-12 Hz), beta- (15-35 Hz) and gamma- (40-80 Hz) band activity, characteristic of previous reports of LFPs in other principle olfactory structures. Beta- and gamma-band powers were enhanced upon odor presentation. Simultaneous recordings of OT and upstream olfactory bulb (OB) LFPs revealed odor-evoked LFP power at statistically similar levels in both structures. Strong spectral coherence was observed between the OT and OB during both spontaneous and odor-evoked states. Furthermore, the OB theta rhythm more strongly cohered with the respiratory rhythm, and respiratory-coupled theta cycles in the OT occurred following theta cycles in the OB. Finally, we found that the animal's internal state modulated LFP activity in the OT. Together, these data provide initial insights into the network activity of the OT in the awake rat, including spontaneous rhythmicity, odor-evoked modulation, connectivity with upstream sensory input, and state-dependent modulation.

Inhibition of the pontine Kölliker-Fuse nucleus abolishes eupneic inspiratory hypoglossal motor discharge in rat

The pontine Kölliker-Fuse nucleus (KF) has established functions in the regulation of inspiratory–expiratory phase transition and the regulation of upper airway patency via laryngeal valving mechanisms. Here we studied the role of the KF in the gating and modulation of eupneic hypoglossal motor activity (HNA) using the in situ perfused brainstem preparation, which displays robust inspiratory HNA. Microinjection of glutamate into the KF area triggered complex and often biphasic modulation (excitation/inhibition or inhibition/excitation) of HNA. Subsequent transient pharmacological inhibition of KF by unilateral microinjection of GABA-A receptor agonist isoguvacine reduced HNA and while bilateral microinjections completely abolished HNA. Our results indicate that mixed and overlapping KF pre-motor neurons provide eupneic drive for inspiratory HNA and postinspiratory vagal nerve activity. Both motor activities have important functions in the regulation of upper airway patency during eupnea but also during various oro-pharyngeal behaviors. These results have potential implications in the contribution of state-dependent modulation of KF hypoglossal pre-motor neurons during sleep–wake cycle to obstructive sleep apnea.

Mammalian Pheromones

Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors.

Substituted 4-phenyl-2-aminoimidazoles and 4-phenyl-4,5-dihydro-2-aminoimidazoles as voltage-gated sodium channel modulators

Voltage-gated sodium channels play an integral part in neurotransmission and their dysfunction is frequently a cause of various neurological disorders. On the basis of the structure of marine alkaloid clathrodin, twenty eight new analogs were designed, synthesized and tested for their ability to block human NaV1.3, NaV1.4 and NaV1.7 channels, as well as for their selectivity against human cardiac isoform NaV1.5, using automated patch clamp electrophysiological assay. Several compounds exhibited promising activities on different NaV channel isoforms in the medium micromolar range and some of the compounds showed also moderate isoform selectivities. The most promising results were obtained for the NaV1.3 channel, for which four compounds were found to possess IC50 values lower than 15 μM. All of the active compounds bind to the open-inactivated states of the channels and therefore act as state-dependent modulators. The obtained results validate the approach of using natural products driven chemistry for drug discovery starting points and represent a good foundation for future design of selective NaV modulators.

State-dependent Modulation of Cortical Synchrony by Vagus Nerve Stimulation in Adult Rats

SUMMARY Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-induced phase modulation at a local network level. Eight adult Wistar rats (270–330 g) were used. Each rat underwent implantation of a VNS system under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same anesthesia as previously. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and the LFP was recorded with a sampling rate of 1000 Hz. Phase-locking values (PLV) between all pairs of electrodes in varied frequency bands were calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. The PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased the PLV in a normal state, particularly in the high-γ band. In an epileptic state, on the other hand, VNS increased the PLV in the high-γ band and decreased the PLV in the δ and low-β bands. These results suggest that VNS modulates neural activities in a band-specific and state-dependent manner so as to keep cortical synchrony within the optimal state.

Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

Event Abstract Back to Event Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells János Brunner1* and János Szabadics1 1 Institute of Experimental Medicine Hungarian Academy of Sciences, Department of Pharmacology, Hungary Backpropagating action potentials (bAPs) and local calcium signals that they trigger are fundamental for dendritic functions. Here we addressed the question what extent the changes of local dendritic membrane properties can contribute to the shaping of the coupling between dendritic action potentials and the local calcium responses. Using a combination of in vitro electrophysiological and confocal imaging techniques we found that activation of dendritic GIRK channels via mGlu2 or GABAB receptors enhanced the bAP¬-triggered calcium signals in the dendrites of dentate gyrus granule cells (GCs). The enhancement of calcium signals was significant only in those dendritic regions, where these receptors are predominantly expressed. Similarly to GIRK channel activation, somatic hyperpolarization by DC current injection (from -64 mV to -77 mV), significantly increased bAP-associated calcium signals in the proximal dendrites. The hyperpolarization was associated with a decrease in the input resistance due to the rectification of the membrane potential of GCs. The effect of hyperpolarization on the calcium signals was maintained when T-type calcium currents were blocked but it decreased when GIRK channels were inhibited. Simultaneous dual somato-dendritic recordings from GCs showed that somatic hyperpolarization accelerated the repolarization phase of dendritic bAP in the proximal region whereas the rising phase and peak amplitude was not affected. We hypothesize that the larger driving force for calcium ions during the faster repolarization can contribute to the increasing in calcium signals. Employment of previously recorded dendritic bAP waveforms from hyperpolarized membrane potential as voltage command evoked larger calcium currents in nucleated patches compared to bAP waveform from the same recording at depolarized membrane potential. Furthermore, addition of native, high-voltage activated, inactivating potassium conductance by somatic dynamic clamp resulted in faster repolarization and increased AP related calcium signals relative to the control (i. e. in the absence of the extra conductance) at the same membrane potential. In conclusion, our results revealed that activation of potassium currents can profoundly enhance dendritic bAP-evoked calcium signals in GC dendrites, thus providing a previously unknown state-dependent modulatory mechanism in dendritic signalization. Keywords: Hippocampus, Dentate Gyrus, granule cell, backpropagating action potential, dendritic calcium, calcium imaging Conference: 4th NAMASEN Training Workshop - Dendrites 2014, Heraklion, Greece, 1 Jul - 4 Jul, 2014. Presentation Type: Poster presentation Topic: dendritic integration and compartmentalization Citation: Brunner J and Szabadics J (2014). Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells. Front. Syst. Neurosci. Conference Abstract: 4th NAMASEN Training Workshop - Dendrites 2014. doi: 10.3389/conf.fnsys.2014.05.00019 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Apr 2014; Published Online: 12 Jun 2014. * Correspondence: Mr. János Brunner, Institute of Experimental Medicine Hungarian Academy of Sciences, Department of Pharmacology, Budapest, 1083, Hungary, brunnerj@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers János Brunner János Szabadics Google János Brunner János Szabadics Google Scholar János Brunner János Szabadics PubMed János Brunner János Szabadics Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Isoform Selective Voltage-Gated Sodium Channel Modulators and the Therapy of Pain

Voltage-gated sodium channels are large transmembrane protein complexes responsible for the propagation and transmission of electrical impulses through nerve, muscle and endocrine cells and cell systems. Dysregulated expression and/or functional changes of ion channel isoforms are found in many associated pathological conditions. In such cases, modulation of voltage gated sodium channels (Na(V) channels) is a recognised approach in medicinal chemistry. Multiple small-molecule active compounds are used for a plethora of Na(V) channel-linked indications, for example epilepsy and CNS disorders, arrhythmia, stroke and pain states such as congenital analgesia/hyperalgesia and neuropathic pain. As existent Na(V) channel modulators suffer mainly from selectivity issues and thus exert significant side effects, novel and selective Na(V) channel modulators would be beneficial. Consequently, the increased research on voltage-gated sodium channels has led to a large number of novel compounds that exploit classic binding site selectivity with state-dependence or functional selectivity. Such compounds offer selective targeting and new possibilities for studying the physiology of Na(V) channels and pathophysiology of the associated ailment conditions. This review consolidates the recent literature on Na(V) 1.3, 1.7 and 1.8 channel isoform selective and/or state-dependent modulators. In particular, their structure-activity relationship is illustrated, especially in the context of selectivity on a particular isoform, and their applicability in the therapy of neuropathic pain is described.

Non-Hebbian Long-Term Potentiation of Inhibitory Synapses in the Thalamus

The thalamus integrates and transmits sensory information to the neocortex. The activity of thalamocortical relay (TC) cells is modulated by specific inhibitory circuits. Although this inhibition plays a crucial role in regulating thalamic activity, little is known about long-term changes in synaptic strength at these inhibitory synapses. Therefore, we studied long-term plasticity of inhibitory inputs to TC cells in the posterior medial nucleus of the thalamus by combining patch-clamp recordings with two-photon fluorescence microscopy in rat brain slices. We found that specific activity patterns in the postsynaptic TC cell induced inhibitory long-term potentiation (iLTP). This iLTP was non-Hebbian because it did not depend on the timing between presynaptic and postsynaptic activity, but it could be induced by postsynaptic burst activity alone. iLTP required postsynaptic dendritic Ca(2+) influx evoked by low-threshold Ca(2+) spikes. In contrast, tonic postsynaptic spiking from a depolarized membrane potential (-50 mV), which suppressed these low-threshold Ca(2+) spikes, induced no plasticity. The postsynaptic dendritic Ca(2+) increase triggered the synthesis of nitric oxide that retrogradely activated presynaptic guanylyl cyclase, resulting in the presynaptic expression of iLTP. The dependence of iLTP on the membrane potential and therefore on the postsynaptic discharge mode suggests that this form of iLTP might occur during sleep, when TC cells discharge in bursts. Therefore, iLTP might be involved in sleep state-dependent modulation of thalamic information processing and thalamic oscillations.

Subthreshold Mechanisms Underlying State-Dependent Modulation of Visual Responses

The processing of sensory information varies widely across behavioral states. However, little is known about how behavioral states modulate the intracellular activity of cortical neurons to effect changes in sensory responses. Here, we performed whole-cell recordings from neurons in upper-layer primary visual cortex of awake mice during locomotion and quiet wakefulness. We found that the signal-to-noise ratio for sensory responses was improved during locomotion by two mechanisms: (1) a decrease in membrane potential variability leading to a reduction in background firing rates and (2) an enhancement in the amplitude and reliability of visually evoked subthreshold responses mediated by an increase in total conductance and a depolarization of the stimulus-evoked reversal potential. Consistent with the enhanced signal-to-noise ratio for visual responses during locomotion, we demonstrate that performance is improved in a visual detection task during this behavioral state.

Novel state-dependent voltage-gated sodium channel modulators, based on marine alkaloids from Agelas sponges

Clathrodin, alkaloid isolated from Agelas sponges, was reported in 1995 as a voltage-gated sodium channel modulator. Here we describe the design and synthesis of conformationally restricted clathrodin analogues incorporating the 4,5,6,7-tetrahydrobenzo[d]thiazol-2-amine moiety and evaluation of their modulatory activities on human voltage-gated sodium channel isoforms Nav1.3, Nav1.4 and Nav1.7, as well as their selectivity against cardiac isoform Nav1.5. Compounds were shown to act as state-dependent modulators of Nav1.3, Nav1.4 and Nav1.7 with IC50 values in the lower micromolar range for the open-inactivated state of the channels. Preliminary structure–activity relationship studies have revealed the importance of hydrophobic interactions for binding to all three tested isoforms. Compound 4e with IC50 value of 8 μM against Nav1.4 represents a novel selective state-dependent Nav1.4 channel modulator.

Breathing and brain state: Urethane anesthesia as a model for natural sleep

Respiratory control differs dramatically across sleep stages. Indeed, along with rapid eye movements (REM), respiration was one of the first physiological variables shown to be modulated across sleep stages. The study of sleep stages, their physiological correlates, and neurobiological underpinnings present a challenge because of the fragility and unpredictability of individual stages, not to mention sleep itself. Although anesthesia has often substituted as a model for a unitary stage of slow-wave (non-REM) sleep, it is only recently that urethane anesthesia has been proposed to model the full spectrum of sleep given the presence of spontaneous brain state alternations and concurrent physiological correlates that appear remarkably similar to natural sleep. We describe this model, its parallels with natural sleep, and its power for studying modulation of respiration. Specifically, we report data on the EEG characteristics across brain states under urethane anesthesia, the dependence of brain alternations on neurotransmitter systems, and the observations on state dependent modulation of respiration.

The dorsomedial striatum encodes net expected return, critical for energizing performance vigor

Decision making requires an actor to not only steer behavior towards specific goals, but also determine the optimal vigor of performance. Current research and models have largely focused on the former problem of how actions are directed, while overlooking the latter problem of how they are energized. Here, we designed a self-paced decision-making paradigm that showed that rats' performance vigor globally fluctuates with the net value of their options, suggesting that they maintain long-term estimates of the value of their current state. Lesions of the dorsomedial (DMS), and to a lesser degree, in the ventral striatum (VS) impaired such state-dependent modulation of vigor, rendering vigor to depend more exclusively on the outcomes of immediately preceding trials. The lesions, however, spared choice biases. Neuronal recordings showed that the DMS is enriched with net-value-coding neurons. In sum, the DMS encodes one's net expected return, which drives the general motivation to perform.

Abstract 92: Understanding The Impact Of Anesthetics On Ischemic Cortical Damage By Inducing Stroke In Awake, Freely Moving Mice

Anesthetics such as isoflurane are commonly used to sedate experimental animals during the induction of stroke. However, there is an abundance of data showing that anesthetics modulate brain excitability, blood flow and vascular tone. Given these diverse effects, it begs the question of to what extent do anesthetics modulate ischemic damage and functional outcome? To better understand the effect of isoflurane on stroke outcome, we developed a protocol for inducing photothrombotic cerebral ischemia in an awake, unanesthetized mouse. This protocol involves temporary attachment of a 1mm diameter plastic fiber optic cable to a previously implanted Luer lock headmount for delivery of photoactivating green laser light (532nm, 1100 mW/cm 2 ) for 15 minutes to the forelimb somatosensory cortex. Evidence for compromised forelimb use is observed within 2 minutes of illumination onset. Histological assessment of ischemic damage and behavioural tests of functional outcome are being examined at different times following stroke induction in awake versus 1.5% isoflurane anesthetized mice. Our preliminary results suggest that infarct volume at 1 and 7 days post-stroke is significantly increased in awake relative to anesthetized mice ( 1 day = 3.4mm 3 ± 0.6 vs. 2.03mm 3 ±0.39; 7 days = 2.97mm 3 +/-0.36 vs. 1.97mm 3 +/-0.19, respectively). Consistent with larger infarct volume, mice that were awake during stroke induction show greater and more persistent deficits in sensory function of the affected forepaw. These experiments will enhance our understanding of whether anesthetics modulate ischemic damage. Further, our simple method for inducing stroke in awake, freely moving animals might be useful for future neuroprotective studies that wish to avoid the potentially confounding effects of anesthetics or examine state-dependent modulation of ischemic damage (e.g. sleep, exercise).

Octopaminergic modulation of neuronal responses to flight-induced naturalistic image sequences

Event Abstract Back to Event Octopaminergic modulation of neuronal responses to flight-induced naturalistic image sequences Diana Rien1, Roland Kern1 and Rafael Kurtz1* 1 Bielefeld University, Neurobiology, Germany Sensory input experienced by animals during behavioral action may differ fundamentally during different states of locomotor activity. Given the limited working range of neurons, adjustments of their sensitivity and stimulus tuning to the current locomotor state might be advantageous. Such state-dependent modulation, which has recently received much attention in various animal models (1), was demonstrated in visual motion-sensitive neurons of different fly species (2-4). The modulation of these neurons is mediated by octopamine, as was recently shown directly by manipulating the activity of a set of octopaminergic neurons (5). Flight or walking activity, as well as application of an octopamine agonist caused enhanced resting activity, shorter latencies in the response to abrupt motion onsets, and larger stimulus-induced responses (2,3,5-10). The strongest response boosts were observed with sustained presentation of high temporal frequencies, thus leading in some studies to a shift in the temporal frequency tuning toward higher values (2,7). However, the functional relevance of these state-dependent changes is unclear, because experimenter-defined stimuli have been used instead of natural optic flow. We assessed the functional significance of octopaminergic neuromodulation for the processing of optic flow as experienced during flight. Naturalistic image sequences were reconstructed based on the head position and gaze orientation during flight (11) and replayed with a panoramic stimulus device (12). We studied how the responses of the V1 neuron in Calliphora vicina to these stimuli are modified by octopaminergic modulation. Spontaneous as well as stimulus- induced spike rates were increased by the octopamine agonist CDM and decreased by an antagonist, epinastine. Moreover, small but consistent shifts in the peak positions of cross- correlograms between the different drug-induced states were present, consistent with an octopamine-induced acceleration of responses to optic flow cues. However, cross-correlations as well as coherence values between the responses recorded in different states of octopaminergic modulation were almost as high as those between traces obtained within one state. Thus, our results suggest that naturalistic optic-flow processing is slightly modified, but not fundamentally altered, by state-dependent neuromodulation. Figure 1

What are the mechanisms for analogue and digital signalling in the brain?

Synaptic transmission in the brain generally depends on action potentials. However, recent studies indicate that subthreshold variation in the presynaptic membrane potential also determines spike-evoked transmission. The informational content of each presynaptic action potential is therefore greater than initially expected. The contribution of this synaptic property, which is a fast (from 0.01 to 10 s) and state-dependent modulation of functional coupling, has been largely underestimated and could have important consequences for our understanding of information processing in neural networks. We discuss here how the membrane voltage of the presynaptic terminal might modulate neurotransmitter release by mechanisms that do not involve a change in presynaptic Ca(2+) influx.