Chapter 10 - Infraslow (< 0.1 Hz) oscillations in thalamic relay nuclei: basic mechanisms and significance to health and disease states

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Abstract

In the absence of external stimuli, the mammalian brain continues to display a rich variety of spontaneous activity. Such activity is often highly stereotypical, is 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 infraslow oscillations (ISOs). Whilst this is primarily due to the emergence of functional magnetic resonance imaging (fMRI) as a technique which has revolutionized 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. Last, we consider the relevance of these thalamic ISOs to the pathological activity that occurs in certain types of epilepsy.

Introduction

In the absence of sensory input, the unconstrained brain continues to exhibit a rich array of well-structured, spontaneous activity. Most commonly, this activity consists of prominent periodic signals which are generated by the rhythmic and synchronous discharge of large numbers of cortical neurons. Such signals have been traditionally examined using conventional scalp EEG recording and have been shown to occur within a multitude of overlapping frequency bands ranging from the ~ 0.5 to 4 Hz band that encompasses the slow waves of deep sleep (Crunelli and Hughes, 2010), to the gamma (γ; 30–80 Hz) band and beyond (> 100 Hz) which contain oscillations that are salient to cognitive and attentional processes (Tallon-Baudry, 2009).

In recent years, there has been an increasing interest in brain activities that take place on a much slower timescale than is generally recognized in traditional EEG bands; those which occur at < 0.1 Hz and which are usually referred to as very slow or infraslow oscillations (ISOs). Although the presence of such ISOs has been known about in animals for over 50 years (Aladjalova, 1957), one of the main reasons for the current surge of interest is the consistent finding from human fMRI studies that during the resting state the brain exhibits prominent fluctuations at < 0.1 Hz in the BOLD signal (Fig. 1a; Damoiseaux et al., 2006, De Luca et al., 2006, Fox and Raichle, 2007, Mantini et al., 2007). These fluctuations identify functional anatomical networks, termed resting state networks (RSNs), which are conserved across subjects (Damoiseaux et al., 2006, De Luca et al., 2006, Mantini et al., 2007). Although there is considerable debate regarding the precise relationship between such cerebral fluctuations and neuronal activity (e.g., see Lee et al., 2010, Leopold, 2010, Logothetis, 2010), it is now clear that at the very least they correlate closely with episodes of faster EEG oscillations in several well-defined, traditional EEG bands (Mantini et al., 2007). For example, activity in a well-characterized posterior RSN, which includes brain regions responsible for visual processing and involves a significant participation of the thalamus (Feige et al., 2005, Goldman et al., 2002, Mantini et al., 2007, Moosmann et al., 2003), is well known to be correlated with changes in the amplitude of EEG α rhythms (Fig. 1b and c). Similar correlations with α band power have also been noted in other RSNs (Laufs et al., 2003, Mantini et al., 2007).

ISOs have also recently been identified in full band electroencephalography (fbEEG) recordings from humans (Monto et al., 2008, Vanhatalo et al., 2004, Vanhatalo et al., 2005). Notably, as with activity in fMRI-defined RSNs, these ISOs are also coupled to conventional, faster EEG oscillations (Vanhatalo et al., 2004). Further, and consistent with a role in modulating large-scale neuronal network excitability, they have been shown to regulate behavioral performance (Monto et al., 2008), organize electrophysiological sleep-related events, and influence the precipitation of certain types of epileptic seizures (Vanhatalo et al., 2004). That cognitive performance, as well as the EEG signatures of sleep and epilepsy, can recur on an infraslow timescale is of course not new. For example, generalized polyspikes in patients with the catastrophic Lennox-Gastaut syndrome (LGS) occur significantly more frequently during the active phase of the so-called cyclic alternating pattern (CAP; Eisensehr et al., 2001), an ISO with a periodicity of ~ 20–40 s that participates in the dynamic organization of non-rapid eye movement (NREM) sleep EEG architecture (Terzano and Parrino, 2000). However, that such infraslow fluctuations might occur because of underlying fluctuations in macroscopic excitability is important because it implies that rather than being simply an emergent property of the immediate neuronal networks under scrutiny, these fluctuations are likely to be driven by a more extrinsic source.

As alluded to above, ISOs were first described in the animal brain in a study published over 50 years ago detailing gross electrophysiological recordings from the neocortex of rabbits (Aladjalova, 1957). In this seminal study, two main oscillations were described having periodicities of around 10 and 30–90 s, respectively (Fig. 2a). These oscillations were present at distinct cortical sites, were not synchronized between hemispheres, and in the case of the faster rhythm, could group periods of more conventional EEG oscillations as described above for humans. More recently, activity fluctuations at < 0.1 Hz have also been identified in the visual cortex of the monkey (Leopold et al., 2003) as well as in both the visual and auditory cortices of the rat (Filippov, 2005, Filippov and Frolov, 2005, Filippov et al., 2007, Filippov et al., 2008). Under certain conditions, monkeys and rats also exhibit infraslow fluctuations in the resting BOLD signal (Lu et al., 2007, Vincent et al., 2007).

Apart from the neocortex, ISOs, as evidenced in either local field potentials (LFPs) or neuronal activity, have also been observed in the hippocampus (Penttonen et al., 1999), basal ganglia (Hutchison et al., 2004, Ruskin et al., 1999a, Ruskin et al., 1999b, Zuo et al., 2011), locus coeruleus (Filippov et al., 2004), dorsal raphe (Filippov et al., 2004), olivary pretectal nucleus (Szkudlarek et al., 2008), and in particular, the thalamus (Albrecht and Gabriel, 1994, Albrecht et al., 1998, Filippov, 2005, Filippov and Frolov, 2005, Filippov et al., 2007, He, 2003, Lewandowski et al., 2000). For example, in sensory thalamic relay nuclei, ISOs at ~ 0.02–0.3 Hz have been noted in LFP recordings from both the rat lateral geniculate nucleus (LGN; Filippov, 2005, Filippov and Frolov, 2005) and medial geniculate nucleus (MGN; Filippov et al., 2007). In the cat LGN, an ISO is present in LFP recordings, with this oscillation being correlated with fluctuations in the amplitude of ongoing α waves (Fig. 2c and d), in a manner not dissimilar to that seen in the human EEG (Vanhatalo et al., 2004). At the cellular level, neurons in the LGN exhibit an ISO at ~ 0.01 Hz that is present in both freely moving and anesthetized animals (Albrecht and Gabriel, 1994, Albrecht et al., 1998). This oscillation is readily observed in single unit recordings where it comprises episodes of robust firing interspersed with periods of neuronal silence (Fig. 2b). An ISO is also present in thalamic firing during the generation of so-called cyclic paroxysms (Steriade and Contreras, 1995). Cyclic paroxysms are experimental electrographic seizures in cats (Steriade and Contreras, 1995, Steriade and Contreras, 1998) which recur with a periodicity of ~ 40–60 s, involve a combination of slow (~ 2–4 Hz) spike/polyspike wave (SW/PSW) complexes and fast (10–20 Hz) runs, and are similar to the EEG activity that can occur in LGS in humans (Fig. 3a and b).

Taken together, evidence from both human and animal studies points clearly to the fact that oscillatory activity at < 0.1 Hz is a fundamental trait of cerebral functioning. Furthermore, it is apparent from animal studies that ISOs are a particularly integral component of activity in the thalamus (Albrecht and Gabriel, 1994, Albrecht et al., 1998, Filippov, 2005, Filippov and Frolov, 2005, Filippov et al., 2007, He, 2003, Lewandowski et al., 2000). However, despite these obvious conclusions, the mechanisms that might generate these oscillations remain poorly understood. More specifically, whilst the capacity of isolated neuronal circuits to generate oscillations at higher frequencies (e.g., 8–13 Hz α rhythms; Hughes and Crunelli, 2005, Hughes and Crunelli, 2007, Hughes et al., 2004, Lorincz et al., 2008, Lorincz et al., 2009b, and 20–80 Hz γ oscillations, Cunningham et al., 2003, Cunningham et al., 2004, Fisahn et al., 1998, Hajos et al., 2004, Jefferys et al., 1996, Mann et al., 2005, Oren et al., 2006) has been reasonably well characterized, their ability to display activities in the infraslow (< 0.1 Hz) range has not been extensively examined. In the remainder of this chapter, we describe the properties and mechanisms of an ISO that is present in isolated thalamic slices maintained in vitro (Lorincz et al., 2009a; see also Leresche et al., 1991). As observed in vivo, this thalamic ISO (i) is reflected in both the LFP and individual neurons, (ii) coordinates regional oscillations in the α (~ 8–13 Hz) band, and (iii) can be associated with cyclic paroxysms.

Section snippets

Basic manifestation

Following moderate activation of either muscarinic acetylcholine receptors (mAchRs) and/or metabotropic glutamate receptors (mGluRs) with exogenous agonists, a manipulation that renders thalamic slices in a condition more akin to their natural state in vivo, between 10% and 30% of thalamocortical (TC) neurons in the cat LGN, MGN, and ventrobasal (VB) thalamus (i.e., the somatosensory thalamus) exhibit a robust ISO at around 0.03–0.1 Hz (Fig. 4a; Lorincz et al., 2009a). This ISO is evident in

Physiological and pathological significance of ISOs in the thalamus

We have discussed the properties and mechanisms of an ISO that is present in acute slices of cat thalamic relay nuclei. In doing so, we have highlighted a potential key role for astrocytes in its generation. We have also identified two main similarities between the ISO that exists in reduced thalamic preparations with activity that occurs in the intact brain. First, in both thalamic recordings from intact cats and those from acute slices, the ISO is linked to changes in the amplitude of local α

Acknowledgments

This work was supported by the Wellcome Trust grants 71436, 78403, 91882 awarded to V. C. and 78311 awarded to S. W. H.

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  • Cited by (0)

    1

    Current address: Lilly UK, Erl Wood Manor, Windlesham, Surrey, United Kingdom.

    2

    Current address: Instituto Gulbenkian de Ciênca, Rue de Quinta Grande, 6, Oerias, Portugal.

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