Thalamic inhibitory circuits and network activity development

Abstract

Inhibitory circuits in thalamus and cortex shape the major activity patterns observed by electroencephalogram (EEG) in the adult brain. Their delayed maturation and circuit integration, relative to excitatory neurons, suggest inhibitory neuronal development could be responsible for the onset of mature thalamocortical activity. Indeed, the immature brain lacks many inhibition-dependent activity patterns, such as slow-waves, delta oscillations and sleep-spindles, and instead expresses other unique oscillatory activities in multiple species including humans. Thalamus contributes significantly to the generation of these early oscillations. Compared to the abundance of studies on the development of inhibition in cortex, however, the maturation of thalamic inhibition is poorly understood. Here we review developmental changes in the neuronal and circuit properties of the thalamic relay and its interconnected inhibitory thalamic reticular nucleus (TRN) both in vitro and in vivo, and discuss their potential contribution to early network activity and its maturation. While much is unknown, we argue that weak inhibitory function in the developing thalamus allows for amplification of thalamocortical activity that supports the generation of early oscillations. The available evidence suggests that the developmental acquisition of critical thalamic oscillations such as slow-waves and sleep-spindles is driven by maturation of the TRN. Further studies to elucidate thalamic GABAergic circuit formation in relation to thalamocortical network function would help us better understand normal as well as pathological brain development.

Keywords: Delta-brush; EEG development; Sleep-spindle; Slow wave; Spindle-bursts; Thalamic reticular nucleus.

Figure 1.. Developmental timelines of thalamocortical activity and inhibitory circuits in humans and rodents.

Developmental timelines of thalamocortical activity, global brain state, intrinsic cellular property, and connectivity, derived from both in vivo and in vitro studies, are shown for human (top), rodent visual system (middle) and rodent somatosensory system (bottom). Colors indicate the locus: cortex (blue), thalamus (green) and TRN (red). These timelines are based on literature cited in the main text.

Figure 2.. Development of thalamic inhibitory circuits and thalamocortical activity.

Circuit diagrams of developmental changes in intrinsic firing, bursting properties, and synaptic (black lines for excitatory; red for inhibitory) and electrical (zigzag lines) connectivity in relation to thalamocortical network activity and state modulation. (Left) Immature thalamocortical oscillations prevail until the late trimester in pregnancy in humans and until the second postnatal week in rodent visual system. A lack of reliable inhibition in thalamus and cortex allows for recurrent feedback amplification of early thalamocortical oscillations such as spindle-bursts and EGOs. (Middle) Initial emergence of mature thalamocortical activity around term in humans and in the second postnatal week in rodents. Incorporation of inhibitory circuits in thalamocortex, particularly TRN, terminates early oscillations and provides continuous desynchronized activity modulated by behavioral states (e.g. slow/delta oscillations). (Right) Emergence of sleep-spindles around 2–3 months of age in humans and third and fourth postnatal weeks in rodents. Further maturation of thalamic inhibitory circuits, especially emergence of multi-spike bursts in TRN and relay nuclei, is likely the circuit basis of acquiring sleep-spindles. (Bottom) Timelines of developmental transitions in thalamocortical activity in humans and rodents (visual system). GW: gestational week. P: postnatal day.