Disynaptic Inhibition between Neocortical Pyramidal Cells Mediated by Martinotti Cells

Abstract

Reliable activation of inhibitory pathways is essential for maintaining the balance between excitation and inhibition during cortical activity. Little is known, however, about the activation of these pathways at the level of the local neocortical microcircuit. We report a disynaptic inhibitory pathway among neocortical pyramidal cells (PCs). Inhibitory responses were evoked in layer 5 PCs following stimulation of individual neighboring PCs with trains of action potentials. The probability for inhibition between PCs was more than twice that of direct excitation, and inhibitory responses increased as a function of rate and duration of presynaptic discharge. Simultaneous somatic and dendritic recordings indicated that inhibition originated from PC apical and tuft dendrites. Multineuron whole-cell recordings from PCs and interneurons combined with morphological reconstructions revealed the mediating interneurons as Martinotti cells. Martinotti cells received facilitating synapses from PCs and formed reliable inhibitory synapses onto dendrites of neighboring PCs. We describe this feedback pathway and propose it as a central mechanism for regulation of cortical activity.

Selective, State-Dependent Activation of Somatostatin-Expressing Inhibitory Interneurons in Mouse Neocortex

“…It is critical to know how interneurons fire under activated conditions because this provides a context for interpreting the functions of their dynamic properties. For example, recent work has shown that somatostatin-expressing Martinotti cells, similar to the cells we studied here, are powerfully excited by synaptic contacts from repetitively firing pyramidal cells; the Martinotti cells can in turn generate powerful inhibition on those pyramidal cells (Kapfer et al 2007;Silberberg and Markram 2007). These findings lead directly to an important question about Martinotti cells: what are their naturalistic firing properties and relevant synaptic dynamics?…”

“…In addition, these cells share multiple characteristics with other described Martinotti cells, including being somatostatin expressing (Halabisky et al 2006;Ma et al 2006;Oliva Jr et al 2000;Wang et al 2004;Xu et al 2006), receiving facilitating input from pyramidal cells (Silberberg and Markram 2007), and showing spike-rate adaptation (Silberberg and Markram 2007;Wang et al 2004). The cells discussed here were often electrically coupled with one another via gap junctions.…”

“…Other cells either did not have an axon projecting to layer I or the axonal destination could not be determined due to inadequate filling or high background staining. Such morphology is associated with Martinotti cells in the neocortex, which have been shown to be somatostatin positive (Ma et al 2006), show spike-rate adaptation (Ma et al 2006), and have been implicated in robust intracortical inhibition (Kapfer et al 2007;Silberberg and Markram 2007). The 16 layer 1-projecting neurons in our sample included both multipolar and bitufted cells, but there was no correlation between somadendritic patterns and axonal projections to layer 1.…”

Les connexions neuronales en pleine lumière

“…De fait, ces voies de signalisation sont inactivées, à un niveau ou à un autre, dans pratiquement toutes les tumeurs. Cette stratégie originale a permis à Baker et al [1] de montrer que la destruction des cellules sénescentes exprimant p16 Ink4a (et donc le gène suicide) améliorait significativement certains symptômes associés à un vieillissement prématuré dans un modèle murin progéroïde basé sur l'expression d'un allèle hypomorphe de la kinase BubR1 (Bub-R1 Hyp/Hyp ) [4]. Ces travaux font écho à de précédentes études démontrant…”

“…Dans cette Nouvelle, nous nous intéresserons aux interneurones GABAergiques qui expriment la somatostatine et qui représentent 30 % des interneurones GABAergiques corticaux. Ils ciblent préférentiellement les dendrites des cellules pyramidales, contrôlant ainsi l'excitabilité dendritique et l'intégration des entrées synaptiques [4,5]. Mais pour comprendre pleinement le rôle de ces interneurones dans la modulation des réseaux fonctionnels excitateurs, il est également nécessaire de caractériser l'organisation anatomique et fonctionnelle des réseaux inhibiteurs.…”