Intra- and Interhemispheric Propagation of Electrophysiological Synchronous Activity and Its Modulation by Serotonin in the Cingulate Cortex of Juvenile Mice

Abstract

Disinhibition of the cortex (e.g., by GABA -receptor blockade) generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14–20 days), the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7) than in retrosplenial cortex slices (RSC 21.99 ± 2.75 ms, n = 5; p<0.05), which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s). We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere), and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges.

Where is Cingulate Cortex? A Cross-Species View

“…Even though studies in mice and rats have played a key role in elucidating neuronal mechanisms by which cingulate cortex drives behavioural regulation [8], the anatomical partitioning system they most commonly use, as discussed in more detail later, cannot be directly translated to findings in virtually any other species, in terms of both structure and function [10][11][12][13]. Specifically, the nomenclature typically applied in rodents divides cingulate cortex into cingulate area 1 (Cg1)…”

Layer 2/3 Pyramidal Neurons of the Mouse Granular Retrosplenial Cortex and Their Innervation by Cortico-Cortical Axons

“…Epileptiform discharges were evoked by stimulation of layer 1 in the presence of a GABA A blocker (bicuculline 10 µM) and a modified ACSF (see ''Materials and Methods'' section). Under these conditions, large epileptiform discharges are known to propagate from the stimulation point to the ipsilateral layer 2/3 and, through the corpus callosum, to the contralateral cortex (Rovira and Geijo-Barrientos, 2016). All non-LS neurons recorded during the propagation of epileptiform discharges showed large depolarizations which always reached the threshold and provoked action potential burst firing ( Figures 4B,C); in fact, the discharges recorded extracellularly were caused by the firing of non-LS neurons.…”

“…The slices were bathed in a modified ACSF (composition in mM: NaCl 124, KCl 5, PO 4 H 2 Na 1.25, MgCl 2 1, CaCl 2 1.2, NaCO 3 H 26, glucose 10; pH 7.4 when saturated with 95% O 2 and 5% CO 2 ). In modified ACSF and in the presence of 10 µM bicuculline (a GABA A receptor antagonist) the stimulation of layer 1 evokes large oscillatory discharges, which were recorded extracellularly with patch pipettes filled with modified ACSF (Rovira and Geijo-Barrientos, 2016). Modified ACSF and bicuculline were used only in the experiments of propagation of epileptiform activity reported in Figure 4.…”

Properties of the epileptiform activity in the cingulate cortex of a mouse model of LIS1 dysfunction

“…Across experiments, stimulus parameters were stable, with minor adjustments of intensity (100-200 µA, 0.1 ms; see "Methods" for details on stimulus intensity adjustment). In these conditions, single-pulse electrical stimuli (100-200 µA, applied at 0.033 Hz) reliably induced stereotyped responses similar to those associated to seizure events recorded in similar conditions, which are the outcome of the coordinated firing of a local population of neurons (Rovira and Geijo-Barrientos 2016). We refer to this type of activity as epileptiform activity (EA).…”

“…Recordings were obtained under conditions of enhanced excitability (bicuculline 10 µM, 5 mM extracellular K + , and 1.2 mM Ca ++ ; see "Methods"). Following our previous study on epileptiform activity propagation (Rovira and Geijo-Barrientos 2016), we recorded from two different cingulate cortical regions, the anterior cingulate cortex (ACC) and the retrosplenial cortex (RSC; Fig. 1A); these two areas were subdivided further in primary and secondary ACC (pACC and sACC) and dorsal agranular and granular RSC (aRSC and gRSC).…”