Hippocampal Contribution to Ordinal Psychological Time in the Human Brain

The chronology of events in time-space is naturally available to the senses, and the spatial and temporal dimensions of events entangle in episodic memory when navigating the real world. The mapping of time-space during navigation in both animals and humans implicates the hippocampal formation. Yet, one arguably unique human trait is the capacity to imagine mental chronologies that have not been experienced but may involve real events-the foundation of causal reasoning. Herein, we asked whether the hippocampal formation is involved in mental navigation in time (and space), which requires internal manipulations of events in time and space from an egocentric perspective. To address this question, we reanalyzed a magnetoencephalography data set collected while participants self-projected in time or in space and ordered historical events as occurring before/after or west/east of the mental self [Gauthier, B., Pestke, K., & van Wassenhove, V. Building the arrow of time horizontal ellipsis Over time: A sequence of brain activity mapping imagined events in time and space.Cerebral Cortex,29, 4398-4414, 2019]. Because of the limitations of source reconstruction algorithms in the previous study, the implication of hippocampus proper could not be explored. Here, we used a source reconstruction method accounting explicitly for the hippocampal volume to characterize the involvement of deep structures belonging to the hippocampal formation (bilateral hippocampi [hippocampi proper], entorhinal cortices, and parahippocampal cortex). We found selective involvement of the medial temporal lobes (MTLs) with a notable lateralization of the main effects: Whereas temporal ordinality engaged mostly the left MTL, spatial ordinality engaged mostly the right MTL. We discuss the possibility of a top-down control of activity in the human hippocampal formation during mental time (and space) travels.

Building the Arrow of Time ... Over Time: A Sequence of Brain Activity Mapping Imagined Events in Time and Space

Baptiste Gauthier

When moving, the spatiotemporal unfolding of events is bound to our physical trajectory, and time and space become entangled in episodic memory. When imagining past or future events, or being in different geographical locations, the temporal and spatial dimensions of mental events can be independently accessed and manipulated. Using time-resolved neuroimaging, we characterized brain activity while participants ordered historical events from different mental perspectives in time (e.g., when imagining being 9 years in the future) or in space (e.g., when imagining being in Cayenne). We describe 2 neural signatures of temporal ordinality: an early brain response distinguishing whether participants were mentally in the past, the present or the future (self-projection in time), and a graded activity at event retrieval, indexing the mental distance between the representation of the self in time and the event. Neural signatures of ordinality and symbolic distances in time were distinct from those observed in the homologous spatial task: activity indicating spatial order and distances overlapped in latency in distinct brain regions. We interpret our findings as evidence that the conscious representation of time and space share algorithms (egocentric mapping, distance, and ordinality computations) but different implementations with a distinctive status for the psychological "time arrow."

OXFORD UNIV PRESS INC2019

Noradrenaline modulates glutamate-mediated neurotransmission in the rat basolateral amygdala in vitro

Pierre Magistretti, Emilie Pralong

The entorhinal cortex and the amygdala are interconnected structures of the limbic system in which paroxysmal activity occurs during temporal lobe epilepsy. Conflicting evidence shows that noradrenaline (i) inhibits the spreading to other parts of the limbic system of paroxysmal activity generated in the amygdala or the entorhinal cortex, but also (ii) increases glutamatergic transmission in the basolateral amygdala. Given our previous work on the inhibitory effect of noradrenaline on entorhinal cortex neurons, we developed an in vitro slice preparation to study the synaptic transmission in the basolateral amygdala and its modulation by noradrenaline. Noradrenaline reduced the fast excitatory postsynaptic potential (EPSP) by approximately 40% at 100 microM and the slow EPSP by approximately 50% at 50 microM. A similar effect was obtained with the alpha2-agonist UK 14304 at 100 and 50 microM respectively. In contrast, the beta-agonist isoproterenol increased the fast EPSP by approximately 40% at 100 microM and the slow EPSP by approximately 20% at 50 microM. Accordingly, the effect of noradrenaline on the EPSPs was blocked by the alpha2-antagonist yohimbine (10 microM) but not by the alpha1-antagonist prazosine (10 microM) and the beta-antagonist propranolol (10 microM). Noradrenaline (50-100 microM) was ineffective on most (14/16) of the isolated inhibitory postsynaptic potentials (IPSPs). These experiments provide evidence that noradrenaline inhibits the excitatory synaptic response of basolateral amygdala neurons. A pharmacological analysis revealed that the noradrenergic modulation of the excitatory transmission in the basolateral amygdala can be dissected into a predominant alpha2-adrenoreceptor-mediated inhibition and a beta-adrenoreceptor-mediated excitation.

1997

Noradrenaline increases K-conductance and reduces glutamatergic transmission in the mouse entorhinal cortex by activation of alpha 2-adrenoreceptors

Pierre Magistretti, Emilie Pralong

The entorhinal cortex is a gateway to the hippocampus; it receives inputs from several cortical associative areas as well as subcortical areas. Since there is evidence showing that noradrenaline reduces the epileptic activity generated in the entorhinal cortex, we have examined the action of noradrenaline in the superficial layer of the entorhinal cortex, which is the main source of afferents to the hippocampus. In a previous study we showed that noradrenaline hyperpolarized layer II entorhinal cortex neurons and reduced global synaptic transmission via alpha 2-adrenoreceptors. Here we present a detailed analysis of the effect of noradrenaline on membrane resistance and on the pharmacologically isolated postsynaptic potentials in layer II entorhinal cortex neurons of mice. Noradrenaline (50 microM) hyperpolarized most layer II entorhinal cortex neurons. This hyperpolarization corresponded to an outward current with a reversal potential following the Nernst equilibrium potential for potassium. The hyperpolarizing effect of noradrenaline was blocked by 10 microM yohimbine. These observations suggest that noradrenaline activates a potassium conductance via an alpha 2-adrenoreceptor. Noradrenaline (10-50 microM) reversibly reduced the amplitude of the pharmacologically isolated excitatory potentials mediated by both NMDA and alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors, the former being more strongly affected. Again this effect was blocked by 10 microM yohimbine. In contrast, GABAA-mediated synaptic transmission was virtually unaffected by noradrenaline. Thus, noradrenaline appears to strongly inhibit the glutamate-mediated synaptic transmission in the entorhinal cortex without affecting inhibitory post-synaptic potentials. These observations suggest that alpha 2-adrenergic receptor agonists may exert a beneficial effect in the control of hyperexcitability in temporal lobe epilepsy.

1995

Noradrenaline increases K-conductance and reduces glutamatergic transmission in the mouse entorhinal cortex by activation of alpha 2-adrenoreceptors

Pierre Magistretti, Emilie Pralong

1995