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1.  Activity of cortical and thalamic neurons during the slow (<1 Hz) rhythm in the mouse in vivo 
During NREM sleep and under certain types of anaesthesia the mammalian brain exhibits a distinctive slow (<1 Hz) rhythm. At the cellular level this rhythm correlates with so-called UP and DOWN membrane potential states. In the neocortex these UP and DOWN states correspond to periods of intense network activity and widespread neuronal silence, respectively, whereas in thalamocortical (TC) neurons, UP/DOWN states take on a more stereotypical oscillatory form with UP states commencing with a low-threshold Ca2+ potential (LTCP). Whilst these properties are now well recognized for neurons in cats and rats, whether or not they are also shared by neurons in the mouse is not fully known. To address this issue we obtained intracellular recordings from neocortical and TC neurons during the slow (<1 Hz) rhythm in anaesthetized mice. We show that UP/DOWN states in this species are broadly similar to those observed in cats and rats, with UP states in neocortical neurons being characterized by a combination of action potential output and intense synaptic activity whereas UP states in TC neurons always commence with an LTCP. In some neocortical and TC neurons we observed ‘spikelets’ during UP states, supporting the possible presence of electrical coupling. Lastly, we show that upon tonic depolarization, UP/DOWN states in TC neurons are replaced by rhythmic high-threshold (HT) bursting at ~5 Hz, as predicted by in vitro studies. Thus, UP/DOWN state generation appears to be an elemental and conserved process in mammals that underlies the slow (<1 Hz) rhythm in several species, including humans.
doi:10.1007/s00424-011-1011-9
PMCID: PMC3256325  PMID: 21892727
EEG; oscillations; sleep; neocortex; thalamocortical
2.  Differential Spike Timing and Phase Dynamics of Reticular Thalamic and Prefrontal Cortical Neuronal Populations during Sleep Spindles 
The Journal of Neuroscience  2013;33(47):18469-18480.
The 8–15 Hz thalamocortical oscillations known as sleep spindles are a universal feature of mammalian non-REM sleep, during which they are presumed to shape activity-dependent plasticity in neocortical networks. The cortex is hypothesized to contribute to initiation and termination of spindles, but the mechanisms by which it implements these roles are unknown. We used dual-site local field potential and multiple single-unit recordings in the thalamic reticular nucleus (TRN) and medial prefrontal cortex (mPFC) of freely behaving rats at rest to investigate thalamocortical network dynamics during natural sleep spindles. During each spindle epoch, oscillatory activity in mPFC and TRN increased in frequency from onset to offset, accompanied by a consistent phase precession of TRN spike times relative to the cortical oscillation. In mPFC, the firing probability of putative pyramidal cells was highest at spindle initiation and termination times. We thus identified “early” and “late” cell subpopulations and found that they had distinct properties: early cells generally fired in synchrony with TRN spikes, whereas late cells fired in antiphase to TRN activity and also had higher firing rates than early cells. The accelerating and highly structured temporal pattern of thalamocortical network activity over the course of spindles therefore reflects the engagement of distinct subnetworks at specific times across spindle epochs. We propose that early cortical cells serve a synchronizing role in the initiation and propagation of spindle activity, whereas the subsequent recruitment of late cells actively antagonizes the thalamic spindle generator by providing asynchronous feedback.
doi:10.1523/JNEUROSCI.2197-13.2013
PMCID: PMC3834053  PMID: 24259570
4.  The thalamic low-threshold Ca2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks 
During non-rapid eye movement (NREM) sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the EEG. Whilst several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual thalamocortical neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the thalamocortical network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. By using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between thalamus and cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in thalamocortical neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca2+ signals are the only ones that inform corticothalamic synapses of the thalamocortical neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.
doi:10.1098/rsta.2011.0126
PMCID: PMC3173871  PMID: 21893530
thalamic neurons; cortical neurons; probabilistic network model; dendrites; intrinsic calcium signalling
5.  The thalamic low-threshold Ca2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks 
During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca2+ signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.
doi:10.1098/rsta.2011.0126
PMCID: PMC3173871  PMID: 21893530
thalamic neurons; cortical neurons; probabilistic network model; dendrites; intrinsic calcium signalling
6.  Infra-slow (<0.1 Hz) oscillations in thalamic relay nuclei: basic mechanisms and significance to health and disease states 
Progress in brain research  2011;193:145-162.
In the absence of external stimuli the mammalian brain continues to display a rich variety of spontaneous activity. Such activity is often highly stereotypical, invariably rhythmic and can occur with periodicities ranging from a few milliseconds to several minutes. Recently there has been a particular resurgence of interest in fluctuations in brain activity occurring at <0.1 Hz, commonly referred to as very slow or infra-slow oscillations (ISOs). Whilst this is primarily due to the emergence of functional magnetic resonance imaging (fMRI) as a technique which has revolutionised the study of human brain dynamics it is also a consequence of the application of full band electroencephalography (fbEEG). Despite these technical advances the precise mechanisms which lead to ISOs in the brain remain unclear. In a host of animal studies, one brain region that consistently shows oscillations at <0.1 Hz is the thalamus. Importantly, similar oscillations can also be observed in slices of isolated thalamic relay nuclei maintained in vitro. Here, we discuss the nature and mechanisms of these oscillations, paying particular attention to a potential role for astrocytes in their genesis. We also highlight the relationship between this activity and ongoing local network oscillations in the alpha (α) (~8-13 Hz) band, drawing clear parallels with observations made in vivo. Lastly, we consider the relevance of these thalamic ISOs to the pathological activity that occurs in certain types of epilepsy.
doi:10.1016/B978-0-444-53839-0.00010-7
PMCID: PMC3173874  PMID: 21854961
acetylcholine; metabotropic glutamate receptor; EEG; gap junctions; alpha rhythm; epilepsy; adenosine; astrocytes; GIRK channels
7.  Activity of cortical and thalamic neurons during the slow (<1 Hz) rhythm in the mouse in vivo 
Pflugers Archiv  2011;463(1):73-88.
During NREM sleep and under certain types of anaesthesia, the mammalian brain exhibits a distinctive slow (<1 Hz) rhythm. At the cellular level, this rhythm correlates with so-called UP and DOWN membrane potential states. In the neocortex, these UP and DOWN states correspond to periods of intense network activity and widespread neuronal silence, respectively, whereas in thalamocortical (TC) neurons, UP/DOWN states take on a more stereotypical oscillatory form, with UP states commencing with a low-threshold Ca2+ potential (LTCP). Whilst these properties are now well recognised for neurons in cats and rats, whether or not they are also shared by neurons in the mouse is not fully known. To address this issue, we obtained intracellular recordings from neocortical and TC neurons during the slow (<1 Hz) rhythm in anaesthetised mice. We show that UP/DOWN states in this species are broadly similar to those observed in cats and rats, with UP states in neocortical neurons being characterised by a combination of action potential output and intense synaptic activity, whereas UP states in TC neurons always commence with an LTCP. In some neocortical and TC neurons, we observed ‘spikelets’ during UP states, supporting the possible presence of electrical coupling. Lastly, we show that, upon tonic depolarisation, UP/DOWN states in TC neurons are replaced by rhythmic high-threshold bursting at ~5 Hz, as predicted by in vitro studies. Thus, UP/DOWN state generation appears to be an elemental and conserved process in mammals that underlies the slow (<1 Hz) rhythm in several species, including humans.
doi:10.1007/s00424-011-1011-9
PMCID: PMC3256325  PMID: 21892727
EEG; Oscillations; Sleep; Neocortex; Thalamocortical; Electroencephalogram; T-type calcium channel; Thalamus; Neocortical neurons
8.  Thalamic Gap Junctions Control Local Neuronal Synchrony and Influence Macroscopic Oscillation Amplitude during EEG Alpha Rhythms 
Although EEG alpha (α; 8–13 Hz) rhythms are often considered to reflect an “idling” brain state, numerous studies indicate that they are also related to many aspects of perception. Recently, we outlined a potential cellular substrate by which such aspects of perception might be linked to basic α rhythm mechanisms. This scheme relies on a specialized subset of rhythmically bursting thalamocortical (TC) neurons (high-threshold bursting cells) in the lateral geniculate nucleus (LGN) which are interconnected by gap junctions (GJs). By engaging GABAergic interneurons, that in turn inhibit conventional relay-mode TC neurons, these cells can lead to an effective temporal framing of thalamic relay-mode output. Although the role of GJs is pivotal in this scheme, evidence for their involvement in thalamic α rhythms has thus far mainly derived from experiments in in vitro slice preparations. In addition, direct anatomical evidence of neuronal GJs in the LGN is currently lacking. To address the first of these issues we tested the effects of the GJ inhibitors, carbenoxolone (CBX), and 18β-glycyrrhetinic acid (18β-GA), given directly to the LGN via reverse microdialysis, on spontaneous LGN and EEG α rhythms in behaving cats. We also examined the effect of CBX on α rhythm-related LGN unit activity. Indicative of a role for thalamic GJs in these activities, 18β-GA and CBX reversibly suppressed both LGN and EEG α rhythms, with CBX also decreasing neuronal synchrony. To address the second point, we used electron microscopy to obtain definitive ultrastructural evidence for the presence of GJs between neurons in the cat LGN. As interneurons show no phenotypic evidence of GJ coupling (i.e., dye-coupling and spikelets) we conclude that these GJs must belong to TC neurons. The potential significance of these findings for relating macroscopic changes in α rhythms to basic cellular processes is discussed.
doi:10.3389/fpsyg.2011.00193
PMCID: PMC3187667  PMID: 22007176
EEG; gap junctions; electrical synapse; alpha rhythms; acetylcholine; metabotropic glutamate receptor
9.  Thalamic T-type Ca2+ channels and NREM sleep 
Cell calcium  2006;40(2):175-190.
T-type Ca2+ channels play a number of different and pivotal roles in almost every type of neuronal oscillation expressed by thalamic neurones during non-Rapid Eye Movement (NREM) sleep, including those underlying sleep theta waves, the K-complex and the slow (<1 Hz) sleep rhythm, sleep spindles and delta waves. In particular, the transient opening of T channels not only gives rise to the ‘classical’ low threshold Ca2+ potentials, and associated high frequency burst of action potentials, that are characteristically present during sleep spindles and delta waves, but also contributes to the high threshold bursts that underlie the thalamic generation of sleep theta rhythms. The persistent opening of a small fraction of T channels, i.e. ITwindow, is responsible for the large amplitude and long lasting depolarization, or UP state, of the slow (<1 Hz) sleep oscillation in thalamic neurones. These cellular findings are in part matched by the wake-sleep phenotype of global and thalamic-selective CaV3.1 knockout mice that show a decreased amount of total NREM sleep time.
T-type Ca2+ channels, therefore, constitute the single most crucial voltage-dependent conductance that permeates all activities of thalamic neurones during NREM sleep. Since ITwindow and high threshold bursts are not restricted to thalamic neurones, the cellular neurophysiology of T channels should now move away from the simplistic, though historically significant, view of these channels as being responsible only for low threshold Ca2+ potentials.
doi:10.1016/j.ceca.2006.04.022
PMCID: PMC3018590  PMID: 16777223
cortex; thalamus; slow sleep oscillations; sleep spindles; delta waves; alpha rhythm; theta rhythm; ITwindow; Ih; ICAN
10.  NeuReal: an interactive simulation system for implementing artificial dendrites and large hybrid networks 
Journal of neuroscience methods  2007;169(2):290-301.
The dynamic clamp is a technique which allows the introduction of artificial conductances into living cells. Up to now, this technique has been mainly used to add small numbers of ‘virtual’ ion channels to real cells or to construct small hybrid neuronal circuits. In this paper we describe a prototype computer system, NeuReal, that extends the dynamic clamp technique to include i) the attachment of artificial dendritic structures consisting of multiple compartments and ii) the construction of large hybrid networks comprising several hundred biophysically realistic modelled neurons. NeuReal is a fully interactive system that runs on Windows XP, is written in a combination of C++ and assembler, and uses the Microsoft DirectX application programming interface (API) to achieve high-performance graphics. By using the sampling hardware-based representation of membrane potential at all stages of computation and by employing simple look-up tables, NeuReal can simulate over 1000 independent Hodgkin and Huxley type conductances in real-time on a modern personal computer (PC). In addition, whilst not being a hard real-time system, NeuReal still offers reliable performance and tolerable jitter levels up to an update rate of 50 kHz. A key feature of NeuReal is that rather than being a simple dedicated dynamic clamp, it operates as a fast simulation system within which neurons can be specified as either real or simulated. We demonstrate the power of NeuReal with several example experiments and argue that it provides an effective tool for examining various aspects of neuronal function.
doi:10.1016/j.jneumeth.2007.10.014
PMCID: PMC3017968  PMID: 18067972
Dynamic Clamp; Thalamus; Oscillations; Computer Simulation; Gap Junctions
11.  Nucleus- and species-specific properties of the slow (<1 Hz) sleep oscillation in thalamocortical neurons 
Neuroscience  2006;141(2):621-636.
The slow (<1 Hz) rhythm is an EEG hallmark of resting sleep. In thalamocortical (TC) neurons this rhythm correlates with a slow (<1 Hz) oscillation comprising recurring UP and DOWN membrane potential states. Recently, we showed that metabotropic glutamate receptor (mGluR) activation brings about an intrinsic slow oscillation in thalamocortical (TC) neurons of the cat dorsal lateral geniculate nucleus (LGN) in vitro which is identical to that observed in vivo. The aim of this study was to further assess the properties of this oscillation and compare them with those observed in TC neurons of three other thalamic nuclei in the cat (ventrobasal complex, VB; medial geniculate body, MGB; ventral lateral nucleus, VL) and two thalamic nuclei in rats and mice (LGN and VB). Slow oscillations were evident in all of these additional structures and shared several basic properties including, i) the stereotypical, rhythmic alternation between distinct UP and DOWN states with the UP state always commencing with a low-threshold Ca2+ potential (LTCP), and ii) an inverse relationship between frequency and injected current so that slow oscillations always increase in frequency with hyperpolarization, often culminating in delta (δ) activity at ~1-4 Hz. However, beyond these common properties there were important differences in expression between different nuclei. Most notably, 44% of slow oscillations in the cat LGN possessed UP states that comprised sustained tonic firing and/or high-threshold (HT) bursting. In contrast, slow oscillations in cat VB, MGB and VL TC neurons exhibited such UP states in only 16%, 11% and 10% of cases, respectively, whereas slow oscillations in the LGN and VB of rats and mice did so in <12% of cases. Thus, the slow oscillation is a common feature of TC neurons that displays clear species- and nuclei-related differences. The potential functional significance of these results is discussed.
doi:10.1016/j.neuroscience.2006.04.069
PMCID: PMC3016515  PMID: 16777348
EEG; delta waves; T-type calcium channels; metabotropic glutamate receptor
12.  Just a phase they’re going through: the complex interaction of intrinsic high-threshold bursting and gap junctions in the generation of thalamic α and θ rhythms 
Rhythms in the α frequency band (8-13 Hz) are a defining feature of the human EEG during relaxed wakefulness and are known to be influenced by the thalamus. In the early stages of sleep and in several neurological and psychiatric conditions α rhythms are replaced by slower activity in the θ (3-7 Hz) band. Of particular interest is how these α and θ rhythms are generated at the cellular level. Recently we identified a subset of thalamocortical (TC) neurons in the lateral geniculate nucleus (LGN) which exhibit rhythmic high-threshold (>-55 mV) bursting at ~2-13 Hz and which are interconnected by gap junctions (GJs). These cells combine to generate a locally synchronized continuum of α and θ oscillations, thus providing direct evidence that the thalamus can act as an independent pacemaker of α and θ rhythms. Interestingly, GJ coupled pairs of TC neurons can exhibit both in-phase and anti-phase synchrony and will often spontaneously alternate between these two states. This dictates that the local field oscillation amplitude is not simply linked to the extent of cell recruitment into a single synchronized neuronal assembly but also to the degree of destructive interference between dynamic, spatially overlapping, competing anti-phase groups of continuously bursting neurons. Thus, the waxing and waning of thalamic α/θ rhythms should not be assumed to reflect a wholesale increase and reduction, respectively, in underlying neuronal synchrony. We argue that these network dynamics might have important consequences for relating changes in the amplitude of EEG α and θ rhythms to the activity of thalamic networks.
doi:10.1016/j.ijpsycho.2006.08.004
PMCID: PMC3016516  PMID: 17000018
EEG; mu rhythm; dendrites; metabotropic glutamate receptor; gap junctions
13.  Are corticothalamic UP states fragments of wakefulness? 
Trends in neurosciences  2007;30(7):334-342.
The slow (<1 Hz) oscillation, along with its alternating UP and DOWN states in individual neurons, is a defining feature of the EEG during slow-wave sleep. Although this oscillation is well preserved across mammalian species, its physiological role remains unclear. Electrophysiological and computational evidence from cortex and thalamus now indicates that the slow oscillation UP states and the ‘activated’ state of wakefulness are remarkably similar dynamic entities. This is consistent with behavioural experiments suggesting that slow oscillation UP states provide a context for the replay and possible consolidation of previous experience. In this scenario, the T-type Ca2+ channel-dependent bursts of action potentials that initiate each UP state in thalamocortical neurons, might act as triggers for synaptic and cellular plasticity in corticothalamic networks.
doi:10.1016/j.tins.2007.04.006
PMCID: PMC3005711  PMID: 17481741
14.  The slow (<1 Hz) rhythm of non-REM sleep: a dialogue between three cardinal oscillators 
Nature neuroscience  2009;13(1):9-17.
The slow (<1 Hz) rhythm, the most significant EEG signature of non-rapid eye movement (NREM) sleep, is generally viewed as originating exclusively from neocortical networks. Here we argue that the full manifestation of this fundamental sleep oscillation within a corticothalamic module requires the dynamic interaction of three cardinal oscillators: a predominantly synaptically-based cortical oscillator and two intrinsic, conditional thalamic oscillators. The functional implications of this hypothesis are discussed in relation to other key EEG features of NREM sleep, with respect to coordinating activities in local and distant neuronal assemblies and in the context of facilitating cellular and network plasticity during slow wave sleep.
doi:10.1038/nn.2445
PMCID: PMC2980822  PMID: 19966841
15.  Novel modes of rhythmic burst firing at cognitively-relevant frequencies in thalamocortical neurons 
Brain research  2008;1235:12-20.
It is now widely accepted that certain types of cognitive functions are intimately related to synchronized neuronal oscillations at both low (α/θ) (4–7/8–13 Hz) and high (β/γ) (18–35/30–70 Hz) frequencies. The thalamus is a key participant in many of these oscillations, yet the cellular mechanisms by which this participation occurs are poorly understood. Here we describe how, under appropriate conditions, thalamocortical (TC) neurons from different nuclei can exhibit a wide array of largely unrecognised intrinsic oscillatory activities at a range of cognitively-relevant frequencies. For example, both metabotropic glutamate receptor (mGluR) and muscarinic Ach receptor (mAchR) activation can cause rhythmic bursting at α/θ frequencies. Interestingly, key differences exist between mGluR- and mAchR-induced bursting, with the former involving extensive dendritic Ca2+ electrogenesis and being mimicked by a non-specific block of K+ channels with Ba2+, whereas the latter appears to be more reliant on proximal Na+ channels and a prominent spike afterdepolarization (ADP). This likely relates to the differential somatodendritic distribution of mGluRs and mAChRs and may have important functional consequences. We also show here that in similarity to some neocortical neurons, inhibiting large-conductance Ca2+-activated K+ channels in TC neurons can lead to fast rhythmic bursting (FRB) at ~40 Hz. This activity also appears to rely on a Na+ channel-dependent spike ADP and may occur in vivo during natural wakefulness. Taken together, these results show that TC neurons are considerably more flexible than generally thought and strongly endorse a role for the thalamus in promoting a range of cognitively-relevant brain rhythms.
doi:10.1016/j.brainres.2008.06.029
PMCID: PMC2778821  PMID: 18602904
acetylcholine; metabotropic glutamate receptors; lateral geniculate nucleus; intralaminar nuclei; oscillations; EEG; cognition; perception; memory
16.  Cellular dynamics of cholinergically-induced alpha (8-13 Hz) rhythms in sensory thalamic nuclei in vitro 
Although EEG alpha (α) (8-13 Hz) rhythms are traditionally thought to reflect an ‘idling’ brain state, they are also linked to several important aspects of cognition, perception and memory. Here we show that reactivating cholinergic input, a key component in normal cognition and memory operations, in slices of the cat primary visual and somatosensory thalamus, produces robust α rhythms. These rhythms rely on activation of muscarinic receptors and are primarily coordinated by activity in the recently discovered, gap junction (GJ)-coupled subnetwork of high-threshold (HT) bursting thalamocortical (TC) neurons. By performing extracellular field recordings in combination with intracellular recordings of these cells we show that, i) the coupling of HT bursting cells is sparse, with individual neurons typically receiving discernable network input from one or very few additional cells, ii) the phase of oscillatory activity at which these cells prefer to fire is readily modifiable and determined by a combination of network input, intrinsic properties and membrane polarization, and iii) single HT bursting neurons can potently influence the local network state. These results substantially extend the known effects of cholinergic activation on the thalamus and in combination with previous studies show that sensory thalamic nuclei possess powerful and dynamically reconfigurable mechanisms for generating synchronized α activity that can be engaged by both descending and ascending arousal systems.
doi:10.1523/JNEUROSCI.4468-07.2008
PMCID: PMC2778076  PMID: 18199766
acetylcholine; lateral geniculate nucleus; electrical synapses; gap junctions; oscillations; EEG; cognition; memory
17.  Temporal Framing of Thalamic Relay-Mode Firing by Phasic Inhibition during the Alpha Rhythm 
Neuron  2009;63(5):683-696.
Summary
Several aspects of perception, particularly those pertaining to vision, are closely linked to the occipital alpha (α) rhythm. However, how the α rhythm relates to the activity of neurons that convey primary visual information is unknown. Here we show that in behaving cats, thalamocortical neurons in the lateral geniculate nucleus (LGN) that operate in a conventional relay-mode form two groups where the cumulative firing is subject to a cyclic suppression that is centered on the negative α rhythm peak in one group and on the positive peak in the other. This leads to an effective temporal framing of relay-mode output and results from phasic inhibition from LGN interneurons, which in turn are rhythmically excited by thalamocortical neurons that exhibit high-threshold bursts. These results provide a potential cellular substrate for linking the α rhythm to perception and further underscore the central role of inhibition in controlling spike timing during cognitively relevant brain oscillations.
doi:10.1016/j.neuron.2009.08.012
PMCID: PMC2791173  PMID: 19755110
SYSNEURO
18.  ATP-Dependent Infra-Slow (<0.1 Hz) Oscillations in Thalamic Networks 
PLoS ONE  2009;4(2):e4447.
An increasing number of EEG and resting state fMRI studies in both humans and animals indicate that spontaneous low frequency fluctuations in cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component of brain functioning, being known to correlate with faster neuronal ensemble oscillations, regulate behavioural performance and influence seizure susceptibility. Although these oscillations have been commonly indicated to involve the thalamus their basic cellular mechanisms remain poorly understood. Here we show that various nuclei in the dorsal thalamus in vitro can express a robust ISO at ∼0.005–0.1 Hz that is greatly facilitated by activating metabotropic glutamate receptors (mGluRs) and/or Ach receptors (AchRs). This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively. In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba2+-sensitive K+ channels. We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain.
doi:10.1371/journal.pone.0004447
PMCID: PMC2637539  PMID: 19212445
19.  Evidence for electrical synapses between neurons of the nucleus reticularis thalami in the adult brain in vitro 
Thalamus & related systems  2008;4(1):13-20.
It has been conclusively demonstrated in juvenile rodents that the inhibitory neurons of the nucleus reticularis thalami (NRT) communicate with each other via connexin 36 (Cx36)-based electrical synapses. However, whether functional electrical synapses persist into adulthood is not fully known. Here we show that in the presence of the metabotropic glutamate receptor (mGluR) agonists, trans-ACPD (100 μM) or DHPG (100 μM), 15% of neurons in slices of the adult cat NRT maintained in vitro exhibit stereotypical spikelets with several properties that indicate that they reflect action potentials that have been communicated through an electrical synapse. In particular, these spikelets, i) display a conserved all-or-nothing waveform with a pronounced after-hyperpolarization (AHP), ii) exhibit an amplitude and time to peak that are unaffected by changes in membrane potential, iii) always occur rhythmically with the precise frequency increasing with depolarization, and iv) are resistant to blockers of conventional, fast chemical synaptic transmission. Thus, these results indicate that functional electrical synapses in the NRT persist into adulthood where they are likely to serve as an effective synchronizing mechanism for the wide variety of physiological and pathological rhythmic activities displayed by this nucleus.
doi:10.1017/S1472928807000325
PMCID: PMC2515363  PMID: 18701937
Gap junctions; connexin36; mGluRs; EEG rhythms; sleep spindles
20.  Hardwiring goes soft: long-term modulation of electrical synapses in the mammalian brain 
Cellscience  2006;2(3):1-9.
Following certain patterns of electrical activity the strength of conventional chemical synapses in many areas of the mammalian brain can be subject to long-term modifications. Such modifications have been extensively characterised and are hypothesised to form the basis of learning and memory. A recent study in Science now shows that activity-dependent long-term modifications may also occur in the strength of mammalian electrical synapses. This raises the enticing possibility that electrical synapses might also contribute to neural plasticity and challenges the notion that in the mammalian CNS they are a simple mechanism for ‘hardwiring’ discrete neuronal populations.
PMCID: PMC2211424  PMID: 18209745
21.  Novel neuronal and astrocytic mechanisms in thalamocortical loop dynamics. 
In this review, we summarize three sets of findings that have recently been observed in thalamic astrocytes and neurons, and discuss their significance for thalamocortical loop dynamics. (i) A physiologically relevant 'window' component of the low-voltage-activated, T-type Ca(2+) current (I(Twindow)) plays an essential part in the slow (less than 1 Hz) sleep oscillation in adult thalamocortical (TC) neurons, indicating that the expression of this fundamental sleep rhythm in these neurons is not a simple reflection of cortical network activity. It is also likely that I(Twindow) underlies one of the cellular mechanisms enabling TC neurons to produce burst firing in response to novel sensory stimuli. (ii) Both electrophysiological and dye-injection experiments support the existence of gap junction-mediated coupling among young and adult TC neurons. This finding indicates that electrical coupling-mediated synchronization might be implicated in the high and low frequency oscillatory activities expressed by this type of thalamic neuron. (iii) Spontaneous intracellular Ca(2+) ([Ca(2+)](i)) waves propagating among thalamic astrocytes are able to elicit large and long-lasting N-methyl-D-aspartate-mediated currents in TC neurons. The peculiar developmental profile within the first two postnatal weeks of these astrocytic [Ca(2+)](i) transients and the selective activation of these glutamate receptors point to a role for this astrocyte-to-neuron signalling mechanism in the topographic wiring of the thalamocortical loop. As some of these novel cellular and intracellular properties are not restricted to thalamic astrocytes and neurons, their significance may well apply to (patho)physiological functions of glial and neuronal elements in other brain areas.
doi:10.1098/rstb.2002.1155
PMCID: PMC1693082  PMID: 12626003

Results 1-21 (21)