A subcortical inhibitory signal for behavioral arrest in the thalamus

Abstract

Organization of behavior requires rapid coordination of brainstem and forebrain activity. The exact mechanisms of effective communication between these regions are presently unclear. The intralaminar thalamus (IL) probably serves as a central hub in this circuit by connecting the critical brainstem and forebrain areas. Here we found that GABAergic/glycinergic fibers ascending from the pontine reticular formation (PRF) of the brainstem evoke fast and reliable inhibition in the IL thalamus via large, multisynaptic terminals. This inhibition was fine-tuned through heterogeneous GABAergic/glycinergic receptor ratios expressed at individual synapses. Optogenetic activation of PRF axons in the IL of freely moving mice led to behavioral arrest and transient interruption of awake cortical activity. An afferent system with comparable morphological features was also found in the human IL. These data reveal an evolutionarily conserved ascending system which gates forebrain activity through fast and powerful synaptic inhibition of the IL thalamus.

Thalamic Inhibition: Diverse Sources, Diverse Scales

“…Their common, defining feature is the large, multisynaptic terminals in the thalamus which are unlike any other known inhibitory terminal in the forebrain [12,15,14,16] (Fig 3C). We will consider here the following ETI nuclei: the output nuclei of basal ganglia (including substantia nigra pars compacta, SNR; intenal globus pallidus, GPi; the ventral pallidum, VP), the zona incerta (ZI), the anterior pretectal nucleus (APT) and the pontine reticular formation (PRF) (Box 3).…”

“…In this review, we will discuss two putative solutions to this problem: Structural and physiological features of TRN will allow its circuits to shift the spatial and temporal scales of inhibition in various behavioral conditions.Powerful ETI systems [12–16] will provide heterogeneous, nucleus-specific inhibitory control of thalamus involved in a well-defined set of nuclei. …”

“…Powerful ETI systems [12–16] will provide heterogeneous, nucleus-specific inhibitory control of thalamus involved in a well-defined set of nuclei.…”

Glycinergic transmission: glycine transporter GlyT2 in neuronal pathologies

“…In these mice, EGFP (enhanced green fluorescent protein) expression largely overlaps with GlyT2 immunoreactivity in axon terminals, and with glycine immunoreactivity in neuronal somata. EGFP is sufficiently bright to identify glycinergic neurons in fixed tissue and in living slices and, therefore, constitutes an excellent tool for investigating the physiological contribution of glycinergic neurons to central nervous system physiology (for instance, see [5][6][7]). Independent of the detailed anatomical distribution and the exquisite morphological details of glycinergic neurons revealed by EGFP, and even though some minor ectopic expression of the transgene was observed, it seemed clear that the segment of the promoter used in these mice contained the major regulatory elements for correct expression of the transgene and, consequently, this segment could be used to design novel mice expressing the recombinase Cre specifically in glycinergic neurons.…”

“…Indeed, these mice have been generated, and the GlyT2-Cre mice are suitable for the selective targeting of floxed genes and transgenes in glycinergic interneurons of brainstem and spinal cord [6,8]. Data recently obtained in these mice are producing relevant information about the role of subpopulations of glycinergic neurons in processing motor and sensory information [6,[9][10][11][12].…”