Bursting Activity In Neurons Research Articles

A method for bidirectional solution exchange—“Liquid bullet” applications of acetylcholine to α7 nicotinic receptors

Fast solution exchange techniques have revolutionized the study of synaptic transmission and promise to remain an important neuroscience research tool. Here we provide evidence for the hypothesis that using continuous, rapid transitions through an agonist solution can significantly increase the exchange rate around a cell by reducing the diffusion boundary at the membrane. This novel approach of rapid solution exchange during whole-cell recordings – described as a “liquid bullet” (LB) application – takes advantage of a bidirectional solution flow around the cell, allowing for a full solution exchange within a range of several milliseconds. An exchange rate (10–90% rise time) of about 2ms could be achieved during both agonist application and washout. We recorded whole-cell currents from cells expressing the rapidly desensitizing α7 neuronal nicotinic receptor (NNR) subtype that exhibited very fast rise times of around 4–5ms. We further demonstrated the advantages of a LB application over conventional methods by the ability of this method to elicit concentration-dependent responses for rapidly desensitizing compounds that were not measurable with conventional agonist applications. In addition, we illustrate the utility of this approach for frequency-based assays through fast, repeated agonist applications at frequencies of 1Hz and 30Hz. This approach could therefore be useful for the study of rapid agonist–receptor interactions that closely mimic the physiological conditions in the synaptic cleft during bursts of neuronal activity.

Interactive Responses of a Thalamic Neuron to Formalin Induced Lasting Pain in Behaving Mice

Thalamocortical (TC) neurons are known to relay incoming sensory information to the cortex via firing in tonic or burst mode. However, it is still unclear how respective firing modes of a single thalamic relay neuron contribute to pain perception under consciousness. Some studies report that bursting could increase pain in hyperalgesic conditions while others suggest the contrary. However, since previous studies were done under either neuropathic pain conditions or often under anesthesia, the mechanism of thalamic pain modulation under awake conditions is not well understood. We therefore characterized the thalamic firing patterns of behaving mice in response to nociceptive pain induced by inflammation. Our results demonstrated that nociceptive pain responses were positively correlated with tonic firing and negatively correlated with burst firing of individual TC neurons. Furthermore, burst properties such as intra-burst-interval (IntraBI) also turned out to be reliably correlated with the changes of nociceptive pain responses. In addition, brain stimulation experiments revealed that only bursts with specific bursting patterns could significantly abolish behavioral nociceptive responses. The results indicate that specific patterns of bursting activity in thalamocortical relay neurons play a critical role in controlling long-lasting inflammatory pain in awake and behaving mice.

Contextual coding of aggressive signals in weakly electric fish

Event Abstract Back to Event Contextual coding of aggressive signals in weakly electric fish Maurice Chacron1* 1 McGill University, Canada Although serotonergic pathways project unto many sensory brain areas, the consequences of such innervations on information processing are not well understood. We have previously shown that serotonin induces burst activity in pyramidal neurons of the electrosensory lateral line lobe (ELL) of weakly electric fish in vitro, which results in better detection of low frequency stimulus features. Here, to further investigate this effect under more natural conditions, we used an in vivo preparation and recorded from the same neurons in awake, behaving brown ghost fish. Extracellular and sharp electrode intracellular techniques were used to record responses of pyramidal neurons to serotonin after either focal application of serotonin to the molecular layer of ELL or electrical stimulation of raphe nuclei. Sine waves (2-256 Hz) were either applied locally to imitate prey or globally to imitate beats resulting from interaction between fish. Small chirps (i.e., aggressive signals) were produced by brief increases in the electric organ discharge frequency (EOD), whereas big chirps (i.e., courtship signals) were produced by long duration concomitant increases and decreases in EOD frequency and amplitude, respectively. In addition to an increased burst firing in ELL pyramidal neurons, serotonin application resulted in an increased phase locking of responses to low frequency (<64 Hz) sine wave stimuli. Further experiments revealed that serotonin did not alter coding of prey signal (i.e., local sinusoids). These results suggest that enhancement in phase locking during global communication is mediated by a feedback mechanism. Furthermore, serotonin application decreased the variability in timing of the first spike and improved the reliability of response to small chirp stimuli. Together, our findings indicate that serotonin, through burst generation in pyramidal neurons and modulation of a feedback pathway, improves the detection of same sex interactions through two mechanisms: increase reliability of coding of aggressive signals (i.e., small chirp) produced by dominant fish and better detection of low frequency beats generated during same sex interaction. Keywords: aggressive signals, Serotonin, weakly electric fish Conference: Tenth International Congress of Neuroethology, College Park. Maryland USA, United States, 5 Aug - 10 Aug, 2012. Presentation Type: Poster (but consider for student poster award) Topic: Neuromodulation Citation: Chacron M (2012). Contextual coding of aggressive signals in weakly electric fish. Conference Abstract: Tenth International Congress of Neuroethology. doi: 10.3389/conf.fnbeh.2012.27.00370 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: 01 May 2012; Published Online: 07 Jul 2012. * Correspondence: Dr. Maurice Chacron, McGill University, Montreal, Canada, maurice.chacron@mcgill.ca 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 Maurice Chacron Google Maurice Chacron Google Scholar Maurice Chacron PubMed Maurice Chacron 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.

Functional Organization and Adaptability of a Decision-Making Network in Aplysia

Whereas major insights into the neuronal basis of adaptive behavior have been gained from the study of automatic behaviors, including reflexive and rhythmic motor acts, the neural substrates for goal-directed behaviors in which decision-making about action selection and initiation are crucial, remain poorly understood. However, the mollusk Aplysia is proving to be increasingly relevant to redressing this issue. The functional properties of the central circuits that govern this animal’s goal-directed feeding behavior and particularly the neural processes underlying the selection and initiation of specific feeding actions are becoming understood. In addition to relying on the intrinsic operation of central networks, goal-directed behaviors depend on external sensory inputs that through associative learning are able to shape decision-making strategies. Here, we will review recent findings on the functional design of the central network that generates Aplysia’s feeding-related movements and the sensory-derived plasticity that through learning can modify the selection and initiation of appropriate action. The animal’s feeding behavior and the implications of decision-making will be briefly described. The functional design of the underlying buccal network will then be used to illustrate how cellular diversity and the coordination of neuronal burst activity provide substrates for decision-making. The contribution of specific synaptic and neuronal membrane properties within the buccal circuit will also be discussed in terms of their role in motor pattern selection and initiation. The ability of learning to “rigidify” these synaptic and cellular properties so as to regularize network operation and lead to the expression of stereotyped rhythmic behavior will then be described. Finally, these aspects will be drawn into a conceptual framework of how Aplysia’s goal-directed circuitry compares to the central pattern generating networks for invertebrate rhythmic behaviors.

Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT2 melatonin receptor ligand.

Melatonin activates two brain G-protein coupled receptors, MT(1) and MT(2), whose differential roles in the sleep-wake cycle remain to be defined. The novel MT(2) receptor partial agonist, N-{2-[(3-methoxyphenyl) phenylamino] ethyl} acetamide (UCM765), is here shown to selectively promote non-rapid eye movement sleep (NREMS) in rats and mice. The enhancement of NREMS by UCM765 is nullified by the pharmacological blockade or genetic deletion of MT(2) receptors. MT(2), but not MT(1), knock-out mice show a decrease in NREMS compared to the wild strain. Immunohistochemical labeling reveals that MT(2) receptors are localized in sleep-related brain regions, and notably the reticular thalamic nucleus (Rt). Microinfusion of UCM765 in the Rt promotes NREMS, and its systemic administration induces an increase in firing and rhythmic burst activity of Rt neurons, which is blocked by the MT(2) antagonist 4-phenyl-2-propionamidotetralin. Since developing hypnotics that increase NREMS without altering sleep architecture remains a medical challenge, MT(2) receptors may represent a novel target for the treatment of sleep disorders.

Identification of the muscarinic pathway underlying cessation of sleep-related burst activity in rat thalamocortical relay neurons

Modulation of the standing outward current (I (SO)) by muscarinic acetylcholine (ACh) receptor (MAChR) stimulation is fundamental for the state-dependent change in activity mode of thalamocortical relay (TC) neurons. Here, we probe the contribution of MAChR subtypes, G proteins, phospholipase C (PLC), and two pore domain K(+) (K(2P)) channels to this signaling cascade. By the use of spadin and A293 as specific blockers, we identify TWIK-related K(+) (TREK)-1 channel as new targets and confirm TWIK-related acid-sensitve K(+) (TASK)-1 channels as known effectors of muscarinic signaling in TC neurons. These findings were confirmed using a high affinity blocker of TASK-3 and TREK-1, namely, tetrahexylammonium chloride. It was found that the effect of muscarinic stimulation was inhibited by M(1)AChR-(pirenzepine, MT-7) and M(3)AChR-specific (4-DAMP) antagonists, phosphoinositide-specific PLCβ (PI-PLC) inhibitors (U73122, ET-18-OCH(3)), but not the phosphatidylcholine-specific PLC (PC-PLC) blocker D609. By comparison, depleting guanosine-5'-triphosphate (GTP) in the intracellular milieu nearly completely abolished the effect of MAChR stimulation. The block of TASK and TREK channels was accompanied by a reduction of the muscarinic effect on I (SO). Current-clamp recordings revealed a membrane depolarization following MAChR stimulation, which was sufficient to switch TC neurons from burst to tonic firing under control conditions but not during block of M(1)AChR/M(3)AChR and in the absence of intracellular GTP. These findings point to a critical role of G proteins and PLC as well as TASK and TREK channels in the muscarinic modulation of thalamic activity modes.

A Shift in Sensory Processing that Enables the Developing Human Brain to Discriminate Touch from Pain

SummaryWhen and how infants begin to discriminate noxious from innocuous stimuli is a fundamental question in neuroscience [1]. However, little is known about the development of the necessary cortical somatosensory functional prerequisites in the intact human brain. Recent studies of developing brain networks have emphasized the importance of transient spontaneous and evoked neuronal bursting activity in the formation of functional circuits [2, 3]. These neuronal bursts are present during development and precede the onset of sensory functions [4, 5]. Their disappearance and the emergence of more adult-like activity are therefore thought to signal the maturation of functional brain circuitry [2, 4]. Here we show the changing patterns of neuronal activity that underlie the onset of nociception and touch discrimination in the preterm infant. We have conducted noninvasive electroencephalogram (EEG) recording of the brain neuronal activity in response to time-locked touches and clinically essential noxious lances of the heel in infants aged 28–45 weeks gestation. We show a transition in brain response following tactile and noxious stimulation from nonspecific, evenly dispersed neuronal bursts to modality-specific, localized, evoked potentials. The results suggest that specific neural circuits necessary for discrimination between touch and nociception emerge from 35–37 weeks gestation in the human brain.

Smoke Extracts and Nicotine, but not Tobacco Extracts, Potentiate Firing and Burst Activity of Ventral Tegmental Area Dopaminergic Neurons in Mice

Nicotine prominently mediates the behavioral effects of tobacco consumption, either through smoking or when taking tobacco by snuff or chew. However, many studies question the exclusive role of nicotine in these effects. The use of preparations containing all the components of tobacco, such as tobacco and smoke extracts, may be more suitable than nicotine alone to investigate the behavioral effects of smoking and tobacco intake. In the present study, the electrophysiological effects of tobacco and smoke on ventral tegmental area dopaminergic (DA) neurons were examined in vivo in anesthetized wild-type (WT), β2-nicotinic acetylcholine receptor (nAChR) knockout (β2-/-), α4-/-, and α6-/- mice and compared with those of nicotine alone. In WT mice, smoke and nicotine had similar potentiating effects on DA cell activity, but the action of tobacco on neuronal firing was weak and often inhibitory. In particular, nicotine triggered strong bursting activity, whereas no bursting activity was observed after tobacco extract (ToE) administration. In β2-/- mice, nicotine or extract elicited no modification of the firing patterns of DA cells, indicating that extract acts predominantly through nAChRs. The differences between DA cell activation profiles induced by tobacco and nicotine alone observed in WT persisted in α6-/- mice but not in α4-/- mice. These results would suggest that tobacco has lower addiction-generating properties compared with either nicotine alone or smoke. The weak activation and prominent inhibition obtained with ToEs suggest that tobacco contains compounds that counteract some of the activating effects of nicotine and promote inhibition on DA cell acting through α4β2*-nAChRs. The nature of these compounds remains to be elucidated. It nevertheless confirms that nicotine is the main substance involved in the tobacco addiction-related activation of mesolimbic DA neurons.

Calcium‐activated non‐selective cation currents are involved in generation of tonic and bursting activity in dopamine neurons of the substantia nigra pars compacta

Nigral dopamine neurons are transiently activated by high frequency glutamatergic inputs relaying reward-predicting sensory information. The tonic firing pattern of dopamine cells responds to these inputs with a transient burst of spikes that requires NMDA receptors. Here, we show that NMDA receptor activation further excites the cell by recruiting a calcium-activated non-selective cation current (ICAN) capable of generating a plateau potential. Burst firing in vitro is eliminated after blockade of ICAN with flufenamic acid, 9-phenanthrol, or intracellular BAPTA. ICAN is likely to be mediated by a transient receptor potential (TRP) channel, and RT-PCR was used to confirm expression of TRPM2 and TRPM4mRNA in substantia nigra pars compacta.We propose that ICAN is selectively activated during burst firing to boost NMDA currents and allow plateau potentials. This boost mechanism may render DA cells vulnerable to excitotoxicity.

In vivo effects of pardoprunox (SLV308), a partial D2/D3 receptor and 5‐HT1A receptor agonist, on rat dopamine and serotonin neuronal activity

The nonergot ligand pardoprunox (SLV308) is a dopamine (DA) D₂/D₃ and serotonin (5-HT)(1A) receptor agonist and a new candidate for the treatment of Parkinson's disease. We used in vivo electrophysiological paradigm in the rat to assess the effects of pardoprunox on DA neuronal activity in ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) as well as on 5-HT neuronal activity in dorsal raphe nucleus (DRN). In the VTA, pardoprunox (2-20 μg kg⁻¹, i.v.) decreased partially the firing activity of DA neurons. Interestingly, the bursting activity of VTA DA neurons was completely suppressed. This compound both reversed and prevented the inhibition of firing rate induced by the full D₂-like receptor agonist apomorphine, confirming its partial D₂-like receptor agonistic property. Surprisingly in the SNc, pardoprunox (10 μg kg⁻¹, i.v.) either partially or fully suppressed the firing activity in two separate populations of DA neurons. Finally, in the DRN, pardoprunox (5-40 μg kg⁻¹, i.v.) completely suppressed the firing activity of 5-HT neurons. Moreover, the selective 5-HT(1A) receptor antagonist WAY-100,635 prevented and reversed the effects of pardoprunox. The present study shows that pardoprunox acts in the VTA as a potent partial D₂-like receptor agonist reducing preferentially the burst activity linked to the phasic activity of DA neurons. Unexpectedly in the SNc, pardoprunox behaves either as apartial or a full D₂-like receptor agonist. Finally in the DRN, pardoprunox is a potent full 5-HT(1A) receptor agonist. Hence, this in vivo study suggests that pardoprunox represents a promising approach for the treatment of Parkinson's disease.

Cannabinoid transmission in the basolateral amygdala modulates fear memory formation via functional inputs to the prelimbic cortex.

The cannabinoid CB1 receptor system is critically involved in the control of associative fear memory formation within the amygdala-prefrontal cortical pathway. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the prelimbic division (PLC) of the medial prefrontal cortex (mPFC). However, the precise role of CB1 receptor transmission within the BLA during the processing of fear memory is not fully understood. We examined the potential role of BLA CB1 receptor transmission during an olfactory fear-conditioning procedure in rats by pharmacologically modulating CB1 cannabinoid transmission directly within the BLA. We report that blockade of BLA CB1 receptor transmission prevents the acquisition of associative fear memory, while having no effect on the recall or consolidation of these memories. In contrast, intra-BLA activation of CB1 receptor transmission or blockade of endocannabinoid reuptake strongly potentiated the emotional salience of normally subthreshold fear-conditioning stimuli. In addition, pharmacological inactivation of the mPFC before intra-BLA CB1 activation blocked CB1-receptor-mediated potentiation of fear memory formation. In vivo single-unit electrophysiological recordings within the PLC revealed that modulation of BLA CB1 receptor transmission strongly influences neuronal activity within subpopulations of PLC neurons, with blockade of intra-BLA CB1 receptor transmission inhibiting spontaneous PLC neuronal activity and activation of CB1 receptors producing robust activation, in terms of neuronal firing frequency and bursting activity. Thus, cannabinoid transmission within the BLA strongly modulates the processing of associative fear memory via functional interactions with PLC neuronal populations.

Parthenolide Blocks Cocaines Effect on Spontaneous Firing Activity of Dopaminergic Neurons in the Ventral Tegmental Area

Chronic cocaine administration leads to catecholamine reuptake inhibition which enhances reward and motivational behaviors. Ventral Tegmental Area dopaminergic (VTA DA) neuronal firing is associated with changes in reward predictive signals. Acute cocaine injections inhibit putative VTA DA cell firing in vertebrates. Parthenolide, a compound isolated from the feverfew plant (Tanacetum parthenium), has been shown to substantially inhibit cocaine’s locomotion effects in a planarian animal model (Pagán et al., 2008). Here we investigated the effects of parthenolide on the spontaneous firing activity of putative VTA DA neurons in anesthetized male rats (250-300g). Single-unit recordings were analyzed after intravenous (i.v.) parthenolide administration followed by 1mg/kg i.v. cocaine injection. Results showed that parthenolide at 0.125 mg/kg and 0.250mg/kg significantly blocked cocaine’s inhibitory effect on DA neuronal firing rate and bursting activity (p< 0.05, two way ANOVA). We propose that parthenolide might inhibit cocaine’s effects on VTA DA neurons via its interaction with a common binding site at monoamine transporters. It is suggested that parthenolide could have a potential use as an overdose antidote or therapeutic agent to cocaine intoxication.

Role of Striatum in the Pause and Burst Generation in the Globus Pallidus of 6-OHDA-Treated Rats

Electrophysiological studies in patients and animal models of Parkinson's disease (PD) often reported increased burst activity of neurons in the basal ganglia. Neurons in the globus pallidus external (GPe) segment in 6-hydroxydopamine (6-OHDA)-treated hemi-parkinsonian rats fire with strong bursts interrupted by pauses. The goal of this study was to evaluate the hypothesis that dopamine (DA)-depletion increases burst firings of striatal (Str) neurons projecting to the GPe and that the increased Str–GPe burst inputs play a significant role in the generation of pauses and bursts in GPe and its projection sites. To evaluate this hypothesis, the unitary activity of Str and GPe was recorded from control and 6-OHDA-treated rats anesthetized with 0.5–1% isoflurane. The occurrence of pauses and bursts in the firings of GPe neurons was significantly higher in 6-OHDA than in normal rats. Muscimol injection into the Str of 6-OHDA rats increased average firing rate and greatly reduced the pauses and bursts in GPe. Recordings from Str revealed that most of the presumed projection neurons in control rats have very low spontaneous activity, and even the occasional neurons that did exhibit spontaneous burst firings did so with an average rate of less than 2 Hz. In DA-depleted Str, neurons having stronger bursts and a higher average firing rate were encountered more frequently. Juxtacellular labeling revealed that most of these neurons were medium spiny neurons projecting only to GPe. Injection of a behaviorally effective dose of methyl-l-DOPA into the Str of 6-OHDA rats significantly increased the average firing rate and decreased the number of pauses of GPe neurons. These data validate the hypothesis that DA-depletion increases burst firings of Str neurons projecting to the GPe and that the increased Str–GPe burst inputs play a significant role in the generation of pauses and bursts in GPe. These results suggest that treatment to reduce burst Str–GPe inhibitory inputs may help to restore some PD disabilities.

Firing pattern regulation in hypothalamic vasopressin neurons: roles of synaptic inputs and retrograde signaling

Magnocellular neurosecretory cells (MNCs) of the hypothalamus release the hormones oxytocin (OT) and vasopressin (VP) into the blood. These cells demonstrate enhancement of hormone release with bursting patterns of electrical activity. OT neurons fire synchronized bursts at long intervals during parturition and milk ejection; VP neurons generate an asynchronous phasic bursting in response to osmotic and cardiovascular stimuli. The mechanisms of bursting activity in VP are not known completely and are believed to be different in vitro and in vivo. Whereas in vitro, phasic bursting in VP neurons appears to be governed by intrinsic deterministic mechanisms, in vivo burst generation and termination significantly depends on synaptic activity. Mounting evidences suggest that retrograde signaling via endocannabinoids (eCBs) plays a prominent role in modulating MNC synaptic activity [1]. Our recent experiments suggest that bursts of action potentials are capable of suppressing glutamatergic input in VP neurons. We also found that blocking eCB receptors increased burst duration and intra-burst action potential frequency, consistent with a potential role in burst termination. To investigate theoretically the role of synaptic inputs in the phasic bursting activity in VP neurons, we used an updated multicompartmental model of the MNC [2]. The model takes into account MNC morphology and electrotonic properties and includes a set of realistic voltage-gated and Ca 2+ -activated ion currents, compartmental Ca 2+ dynamics and reproduces several of the hallmark characteristics of MNC electrophysiological properties. Phasic bursting in the model is controlled by both intrinsic and synaptic mechanisms: bursts of action potentials arise from the summation of slow depolarizing afterpotentials superimposed on a tonic background activation of glutamatergic synaptic inputs; activitydependent release of a retrograde messenger (eCB) from the dendrites of VP neurons attenuates tonic glutamate release and leads to burst termination. Background synaptic activity was simulated as independent excitatory and inhibitory inputs mediated by AMPA and GABAA conductances. Our computational studies also suggest that GABAA receptor activation promotes burst firing patterns, and stochastic synaptic inputs play an important role in the modulation of phasic activity in VP neurons.

Electrophysiological characterization of harmane-induced activation of mesolimbic dopamine neurons

It has been suggested that the beta-carbolines harmane and norharmane may be involved in the pathophysiology of Parkinson's disease, psychosis and addiction, but the mechanisms of these possible effects remain to be elucidated. In the present study, the effects of the two compounds were examined by using in vivo extracellular recordings of ventral tegmental dopamine neurons. The effects of harmane (2 mg/kg) and norharmane (2 mg/kg), were compared to those of nicotine (11 µg/kg), of cotinine (0.5 mg/kg), of the monoamine-oxidase-A inhibitor befloxatone (0.12 mg/kg), and of the monoamine-oxidase-B inhibitor selegiline (0.5 mg/kg). The effects of harmane were also tested after pre-treatment with the nicotine receptor antagonist mecamylamine. The results show that all substances, except befloxatone, activate the firing and/or burst activity of dopamine neurons. The increase in firing rate produced by harmane was approximately 18 times greater than that produced by nicotine. Such powerful excitation of dopamine neurons by harmane may in part explain its involvement in neurotoxicity, psychosis and addiction. The absence of effect of befloxatone supports the hypothesis that the effect of harmane is not related to its monoamine-oxidase-A inhibitory properties. Mecamylamine inhibited by approximately 80% the activity of harmane, indicating that the activating effect of harmane on dopamine neurons involves several mechanisms, among which activation of nicotinic receptors likely has a prominent importance. The results of the present study support the hypothesis that harmane could be a tobacco (or smoke) component other than nicotine involved in tobacco dependence.

Excitotoxic-mediated transcriptional decreases in HCN2 channel function increase network excitability in CA1

Changes in the conductance of the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel that mediates I h are proposed to contribute to increased network excitability. Synchronous neuronal burst activity is a good reflection of network excitability and can be generated in isolated hippocampal slice cultures by removing Mg 2+ from the extracellular fluid. We demonstrate that I h contributes to this activity by increasing both the frequency and duration of bursting events. Changes in HCN channel function are also implicated in altered seizure susceptibility. Short-term application of kainic acid (KA) is known to initiate long lasting changes in neuronal networks that result in seizures, and in slice cultures was found to alter HCN mRNA levels in an isoform and hippocampal sub-region specific manner. These changes correlate with the ability of each sub-region to develop synchronous burst activity following KA that we have previously reported. Specifically, a loss of synchronous activity in the CA3 correlated with an increase in HCN2 mRNA levels that normalized concomitantly with the restoration of CA3 burst activity 7 days post insult. In contrast, in CA1 an increase in synchronous burst duration correlated with a reduction in HCN2 mRNA levels and both changes were still evident for 7 days post insult. Lamotrigine, known to increase I h, reversed the impact of KA on burst duration in CA1 at both time-points linking a transcriptional reduction in HCN2 function to increased burst duration.

Statistical Long-Term Correlations in Dissociated Cortical Neuron Recordings

The study of nonlinear long-term correlations in neuronal signals is a central topic for advanced neural signal processing. In particular, the existence of long-term correlations in neural signals recorded via multielectrode array (MEA) could provide interesting information about changes in interneuron communications. In this study we propose a new method for long-term correlation analysis of neuronal burst activity based on the periodogram alpha slope estimation of the MEA signal. We applied our method to recordings taken from cultured networks of dissociated rat cortical neurons. We show the effectiveness of the method in analyzing the activity changes as well as the temporal dynamics that take place during the development of such cultures. Results demonstrate that the alpha parameter is able to divide the network development in three well-defined stages, showing pronounced variations in the long-term correlation among bursts.

Parkinsonism: evolving pathophysiologic concepts

The link between the hallmark pathology in Parkinson's disease, i.e., dopamine loss in the basal ganglia, and the behavioral signs of parkinsonism, remains mysterious. This presentation will review our knowledge of system-level changes in brain activity in parkinsonism. The most commonly discussed models of the changes in brain activity that lead to parkinsonism were developed twenty years ago, and were strongly based on anatomical considerations and changes in the firing rates of basal ganglia neurons in dopamine-depleted animals. The most important change noted was an increase in the activity of neurons in the basal ganglia output nuclei. A simple anatomic argument was used to link these changes to the striatal loss of dopamine. Since that time, a plethora of new findings has emerged, indicating that the changes in firing rate may be less important than changes in other aspects of basal ganglia activity. Changes in oscillatory activity in the beta- and gamma-bands of frequencies have been observed to be important, as have changes in non-linear firing characteristics such as increases in the bursting activity of individual basal ganglia neurons. Studies in animals and humans have also shown that the ensemble activity of basal ganglia neurons appears to be altered in parkinsonism, with the emergence of pathological levels of synchronization between neighboring neurons. Perhaps most importantly, parkinsonism has emerged as a circuit disorder in which the focal loss of dopamine in the basal ganglia has significant down-stream effects on the activity of other areas of the brain, specifically the thalamus, portions of the cortex, and the brainstem. Many questions in this field remain unanswered. The links between dopamine loss and the changes in firing patterns have not been identified, and the relationship between the electrical changes in the basal ganglia-thalamocortical circuitry and parkinsonian motor signs remains unclear. The significance of anatomical changes that are secondary to long-term dopamine loss, such as loss of the dendritic spines of striatal medium spiny neurons, and the role of non-dopaminergic or extra-basal ganglia pathology in parkinsonism also need to be elucidated. Addressing these questions will be essential for the development of more effective pharmacological and surgical strategies to treat parkinsonian patients.

Dynamics of two neuronlike elements with inhibitory feedback

An analog electronic model is proposed to qualitatively reproduce the main dynamic regimes of inferior-olive (IO) neurons. An analog simulation is used to study the dynamics of a single IO neuron and a pair of neurons involved in inhibitory feedback. The experimental results that demonstrate that such feedback leads to a partial spike synchronization of the interacting neurons are presented. It is shown that the electronic model can be used for the simulation of the burst activity of oscillatory neurons.

Sleep and sensorimotor integration during early vocal learning in a songbird

Behavioural studies widely implicate sleep in memory consolidation in the learning of a broad range of behaviours1-4. During sleep, brain regions are reactivated5,6, and specific patterns of neural activity are replayed7-10, consistent with patterns observed in prior waking behaviour. Birdsong learning is a paradigmatic model system for skill learning11-14. Song development in juvenile zebra finches is characterised by sleep-dependent circadian fluctuations in singing behaviour, with immediate post-sleep deterioration in song structure followed by recovery later in the day15. In sleeping adult birds, spontaneous bursting activity of forebrain premotor neurones in the robust nucleus of the arcopallium (RA) carries information about daytime singing16. Here we show that in juvenile zebra finches, playback during the day of an adult “tutor” song induced profound and tutor song-specific changes in bursting activity of RA neurones during the following night of sleep. The night-time neuronal changes preceded tutor song-induced changes in singing, first observed the following day. Interruption of auditory feedback greatly reduced sleep bursting and prevented the tutor song-specific neuronal remodelling. Thus, night-time neuronal activity is shaped by the interaction of the song model (sensory template) and auditory feedback, with changes in night-time activity proceeding the onset of practice associated with vocal learning. We hypothesise that night-time bursting induces adaptive changes in premotor networks during sleep as part of vocal learning. By this hypothesis, plastic changes are driven by replay of sensory information at night and evaluation of sensory feedback during the day, with the interaction between the two leading to complex circadian patterns such as are seen early in vocal development.