Thalamic Inhibition: Diverse Sources, Diverse Scales

Abstract

The thalamus is the major source of cortical inputs shaping sensation, action and cognition. Thalamic circuits are targeted by two major inhibitory systems: the thalamic reticular nucleus (TRN) and extra-thalamic inhibitory (ETI) inputs. A unifying framework of how these systems operate is currently lacking. Here, we propose that TRN circuits are specialized to exert thalamic control at different spatiotemporal scales. Local inhibition of thalamic spike rates prevails during attentional selection whereas global inhibition more likely during sleep. In contrast, the ETI (arising from basal ganglia, zona incerta, anterior pretectum and pontine reticular formation) provides temporally-precise and focal inhibition, impacting spike timing. Together, these inhibitory systems allow graded control of thalamic output, enabling thalamocortical operations to dynamically match ongoing behavioral demands.

The relationship between thalamic GABA content and resting cortical rhythm in neuropathic pain

“…It is possible that mechanisms other than the circuit with the TRN could be responsible for the findings we report on; however, we think it less likely to be these sources than the TRN. As well as our previous finding of decreased cerebral blood flow in the TRN in neuropathic pain (Henderson et al, 2013), extrathalamic inhibitory nuclei do not exhibit recurrent circuits with the thalamus (i.e., they have no thalamic inputs), nor do they directly innervate the primary somatosensory thalamus (Bartho et al, 2002;Bokor et al, 2005;Halassa & Acsady, 2016).…”

Memantine protects thalamocortical hyper‐glutamatergic transmission induced by NMDA receptor antagonism via activation of system xc−

“…Glutamatergic neurons in the MDTN, which receive GABAergic terminals from the reticular thalamic nucleus (RTN) and other MDTN regions, project to superficial layers in the frontal cortex . Moreover, thalamocortical glutamatergic terminals activate catecholaminergic terminals, but do not make contact with cortical GABAergic neurons .…”

“…23 Glutamatergic neurons in the MDTN, which receive GABAergic terminals from the reticular thalamic nucleus (RTN) and other MDTN regions, project to superficial layers in the frontal cortex. [37][38][39] Moreover, thalamocortical glutamatergic terminals activate catecholaminergic terminals, but do not make contact with cortical GABAergic neurons. 35,36 However, a large proportion of the GABAergic neurons in the frontal cortex are regulated by excitatory glutamatergic transmission from other cortical regions via activation of NMDAR.…”

Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms

“…The nucleus reticularis thalami (nRT) is the “guardian of the gateway” in the thalamocortical circuit, given its role in modulating interactions between the cerebral cortex and thalamus (Crick, 1984; Halassa and Acsády, 2016). The nRT modulates thalamocortical oscillations that underlie functions like such as attention, sensation, sleep, and consciousness (Calabrò et al, 2015; Crick, 1984; Steriade, 2005).…”

“…nRT neurons can orchestrate brain-wide network activity (Crick, 1984; Halassa and Acsády, 2016). Brief optogenetic stimulation of nRT neurons in vivo induces spindles in the cortex during non-rapid eye movement sleep (Halassa et al, 2011), while sustained stimulation increases delta band power similar to slow-wave sleep (Lewis et al, 2015).…”