The thalamic reticular nucleus and schizophrenia

Abstract

Background: The thalamic reticular nucleus (TRN) is a shell-shaped gamma amino butyric acid (GABA)ergic nucleus, which is uniquely placed between the thalamus and the cortex, because it receives excitatory afferents from both cortical and thalamic neurons and sends inhibitory projections to all nuclei of the dorsal thalamus.

Method: A review of the evidence suggesting that the TRN is implicated in the neurobiology of schizophrenia.

Results: TRN-thalamus circuits are implicated in bottom-up as well as top-down processing. TRN projections to nonspecific nuclei of the dorsal thalamus mediate top-down processes, including attentional modulation, which are initiated by cortical afferents to the TRN. TRN-thalamus circuits are also involved in bottom-up activities, including sensory gating and the transfer to the cortex of sleep spindles. Intriguingly, deficits in attention and sensory gating have been consistently found in schizophrenics, including first-break and chronic patients. Furthermore, high-density electroencephalographic studies have revealed a marked reduction in sleep spindles in schizophrenics.

Conclusion: On the basis of our current knowledge on the molecular and anatomo-functional properties of the TRN, we suggest that this thalamic GABAergic nucleus may be involved in the neurobiology of schizophrenia.

Fig. 1.

Connectivity Between The Cortex, The Thalamic Reticular Nucleus (TRN), and The Thalamus. The asterisk indicates a cortex-TRN-thalamus circuit thought to be involved in lateral inhibition (see text).

Fig. 2.

Spindles Deficits in Schizophrenics Have High Effect Size (ES); Can Be Detected With A Few Electroencephalographic (EEG) Channels; and Correlate With Clinical Symptoms. (A) The top trace shows 20 s of non-rapid eye movement (NREM) sleep, with vertical lines enclosing sleep spindles. The bottom trace represents the rectified EEG signal filtered in the spindle range (12–16 Hz). Circles indicate the beginning and end of each spindle, as well as its maximal amplitude, while the highlighted area reflects spindle activity integrated over time (ISA). (B) Left panel: high-density (185 channels) topography of the ES of spindle deficits in schizophrenics. Spindle deficits had high ES, corresponding to 85% separation between schizophrenics and control subjects. Similar ES were obtained with a 14-channel EEG montage (middle panel), and they were correlated with the clinical symptoms of schizophrenics (right panel).

Fig. 3.

Pharmacological Models of Psychosis Induced by NMDA Antagonists (eg, PCP) or by Deficits of TRN Gamma Amino Butyric Acid (GABA)ergic Neurons. Left panel: PCP blocks (X) NMDA receptors in the Cortex, TRN, and Thalamus. The overall effect is a reduction in TRN GABA release, which results in an increase in the activity of cortex-thalamus and thalamus-cortex α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) excitatory synapses. Right panel: deficits in TRN GABAergic neurons (X) can induce a similar increase in the activity of cortex-thalamus and thalamus-cortex connections, which is mediated by both AMPA and NMDA synapses.