Spontaneous Activity

The following review is motivated by the hypothesis put forward by Benuskova and her colleagues that an ongoing pre- and postsynaptic background activity determines not only the degree of input-specific LTP elicited by various plasticity-inducing protocols, but also the degree of associated LTD in neighbouring non-tetanized inputs (Benuskova and Abraham, 2007; Abraham et al., 2007; Benuskova and Jedlicka, 2012; Jedlicka et al., 2015; Shirrafiardekani et al., 2019). These associated
changes are considered to be “heterosynaptic“, i.e. different-synaptic as opposed to “homosynaptic” i.e. the same-synaptic. This raises the question – what do we consider to be an input activity? Through the course of evolution, nature has been able to eliminate nonessential processes that would waste energy, and since such a large part of neural activity is not directly derived from sensory channels and can be considered spontaneous or background – what is its function? As we will later show, spontaneous activity is a homeostatic process and is, as such, a constitutive restriction in establishing synapse strength, therefore a sort of input. Understanding regularities of ongoing activity can help us define boundary conditions for both LTP and LTD induction and their maintenance.

The goal of the following review is to revisit experimental studies of plasticity in slices (in vitro) and in vivo with respect to the effect of various anaesthetics on ongoing activity. Experimental data used is collected from studies that dealt with such processes in excitatory glutamate synapses which are found in granule cells of the dentate gyrus, neurons in the CA1 region of the hippocampus (HPC), and various cortical (CTX) networks. A large majority of data is collected from mammalian tissues, but we will occasionally support our claims with studies done on amphibian and fish tissues. In order to give a nuanced picture, we will also be drawing results from computational models of synaptic plasticity, developmental and pathophysiological studies and behavioural data.

Firstly, we will address the mechanisms of LTP and LTD induction in excitatory glutamate synapses, the interrelatedness of the two and, briefly, non-glutamate mechanisms by which synaptic weight changes occur. Then we will assess the role of spontaneous activity in regulating their respective degrees and how much the in vitro conditions can reflect its effect, since the scope of spontaneous activity is limited there. Thirdly, we will see how anaesthetics affect the capacity for LTP and LTD induction and maintenance, mostly with “high-specificity” studies. Lastly, we will inquire into how spontaneous activity is affected by various types of anaesthetics and what that means for ethological validity of in vivo studies of LTP/LTD in which anaesthetics are used due to ethical requirements. We will try to draw conclusions on what all of the above indicates, while keeping methodological restrictions in mind.

[French abstract:] Le cerveau produit une consommation importante d’énergie dont nous ne savons toujours pas précisément à quelle fin elle est utilisée. Nommée « énergie noire » en référence aux découvertes des astrophysiciens, cette énergie est mesurable par l’activité spontanée d’un sujet même privé de cognition consciente. Ainsi, contrairement aux idées reçues, le cerveau ne serait pas silencieux en l'absence de stimulations sensorielles et ne réagirait pas de façon réflexive aux stimuli extérieurs. Les fluctuations de cette activité spontanée correspondraient à une dynamique intrinsèque du cerveau qui ne s'arrêterait jamais de générer des hypothèses sur les représentations qu’il se fait du monde. Dans cet article, les auteurs proposent un résumé des connaissances acquises sur le sujet et ouvrent une nouvelle voie de recherche.

[English abstract:] The brain uses a large amount of energy, the function of which is still not fully known. Called ‘dark energy’, with reference to the recent discoveries by astrophysicists, this energy is measured by the spontaneous activity of a patient even if when they are deprived of conscious cognition. Thus, contrary to generally accepted ideas, the brain would not be silent in the absence of sensory stimulation and would not respond reflexively to external stimuli. The fluctuations in this spontaneous activity correspond to an inbuilt dynamic in the brain, which would never stop generating hypotheses about its depiction of the world. In this paper, authors provide a summary of the knowledge gained about the topic, and open up a new field of research.

The "default network" consists of a number of brain regions that exhibit correlated low-frequency activity at rest and that have been suggested to be involved in the processing of self-relevant stimuli. Activity in many of these areas has also been shown to be altered in individuals with posttraumatic stress disorder (PTSD). We hypothesized that the posterior cingulate cortex (PCC)/precuneus, part of the default network, would exhibit altered connectivity at rest with other areas of the default network and regions associated with PTSD. Seventeen medicated and unmedicated female patients with chronic posttraumatic stress disorder (PTSD) related to early-life trauma and 15 healthy female controls underwent a 5.5-minute functional magnetic resonance imaging scan with their eyes closed. We assessed areas of the brain whose activity positively and negatively correlated with that of the PCC/precuneus in both groups. At rest, spontaneous low-frequency activity in the PCC/precuneu...

This study was undertaken to investigate the role of afferent spontaneous electrical activity in regulating death of target cells in the developing mammalian visual system. We show here that naturally occurring cell death in the rat superior colliculus is greatly augmented when the spontaneous firing of retinal ganglion cells is transiently blocked with TTX. An increased number of dying cells is already observed after 1 hr of afferent blockade. A 50% increase of cell death is reached after 3 hr of blockade, an effect that closely parallels increased cell death caused by eye enucleation after similar intervals of time. These results suggest that, during development, input cells exert a trophic action on target cells, which is prevented by silencing input electrical activity. A likely explanation of this effect is that the spontaneous firing of input cells causes the release by afferent fibers of a trophic agent promoting the survival of target cells.

A previous study has shown that lumbar spontaneous cord dorsum potentials (CDPs) are produced by background activity of a neuronal ensemble located in the dorsal horn. Here, the effects produced by intravenous application of the nitric oxide synthase inhibitor L-N(G)-nitro arginine (L-NOARG, 100 microg/kg) and of the nitric oxide donor 3-morpholinosydnonimine hydrochloride (SIN-1, 500 microg/kg) on spontaneous CDPs were examined. Experiments were performed on pentobarbitally anesthetized, paralyzed and spinalized cats. The amplitude of spontaneous CDPs increased after L-NOARG, however, decreased after SIN-1. These observations suggest that electrical activity of dorsal horn neurones generating spontaneous CDPs is dependent on nitric oxide production.

Obese boys (n = 10, aged 10- 1 1 y, average percent body fat (%BF) 32.4) were given a regimented training program (4 wk, 5 1-h sessions, 45 mm cycling/wk at 50-60% of predetermined VO2max) to investigate whether they modify their energy expenditure by reducing or augmenting their spontaneous physical activities. No change was observed in mean weight (52.7 vs

Functional magnetic resonance imaging (fMRI) has allowed insights into the spatiotemporal distribution of human brain networks. According to the neurophysiological property of the fetal brain to generate spontaneous activity, we aimed to determine the feasibility of investigating the maturation of intrinsic networks, beginning at gestational week 20 in healthy human fetuses by combining resting-state fMRI and an analytical approach, independent component analysis (ICA). In this study, functional images of 16 fetuses with morphologically normal brain development, from 20 to 36 gestational weeks of age, were acquired on a 1.5T unit (Philips Medical Systems, Best, The Netherlands) using single-shot, gradient-recalled echo-planar imaging. After preprocessing (motion correction, brain extraction), images were analyzed using single-subject ICA. We visualized a bilateral occipital network and medial and lateral prefrontal activity pattern that involved the future Brodmann areas 9-11. Furth...

The relation between the electrophysiological activity of Type I striatal neurons, local dopamine (DA) concentration, and motor behavior in rats was investigated using intraventricular administration of the neurotoxin 6-hydroxydopamine (6-HDA) and extracellular single-unit ...

We examined the relation between ectopic afferent firing and tactile allodynia in the Chung model of neuropathic pain. Transection of the L5 spinal nerve in rats triggered a sharp, four- to six-fold increase in the spontaneous ectopic discharge recorded in vivo in sensory axons in the ipsilateral L5 dorsal root (DR). The increase, which was not yet apparent 16 h postoperatively, was complete by 24 h. This indicates rapid modification of the electrical properties of the neurons. Only A-neurons, primarily rapidly conducting A-neurons, contributed to the discharge. No spontaneously active C-neurons were encountered. Tactile allodynia in hindlimb skin emerged during precisely the same time window after spinal nerve section as the ectopia, suggesting that ectopic activity in injured myelinated afferents can trigger central sensitization, the mechanism believed to be responsible for tactile allodynia in the Chung model. Most of the spike activity originated in the somata of axotomized DRG...