Dysregulation of thalamic sensory ‘transmission’ in schizophrenia: neurochemical vulnerability to hallucinations

Abstract

Cholinergic arousal mechanisms predispose thalamic and cortical neurons to fire action potentials at gamma rhythms, which have a tendency to resonate in thalamocortical networks, thereby forming coherent assemblies under constraints of sensory input to specific thalamic nuclei, on the one hand, and prefrontal and limbic attentional mechanisms, on the other. Perception may be based on sustained assemblies of coherent gamma oscillations in thalamocortical circuits. In schizophrenia, the impact of sensory input on self-organization of thalamocortical activity may be generally reduced. As a result, processes underlying perception can become uncoupled from sensory input, particularly at times of hyperarousal, leading to domination of attentional mechanisms and the emergence of hallucinations. Evidence is reviewed that implicates excessive neuronal noise in specific thalamic nuclei in the generation of hallucinations in schizophrenia. Nicotinic receptor abnormalities, dopaminergic hyperactivity and glutamate-receptor hypofunction are reconciled within a model of psychotic symptom generation that places crucial emphasis on dysfunction of the reticular thalamic nucleus.

Regulation of Inhibitory Synapses by Presynaptic D4 Dopamine Receptors in Thalamus

“…Within thalamic circuitry, DA-dependent actions are thought to play a potentially significant role in emotion, attention, cognition, and complex somatosensory and visual processing (Takahashi et al 2006). Alterations in thalamic DA receptors are also implicated in various neurological and psychiatric disorders (Behrendt 2006;Buchsbaum et al 2006;Di Chiara 2002;Kane et al 2009;Takahashi et al 2006;Yasuno et al 2004). Anatomical studies have shown that TRN receives a dopaminergic innervation from the substantia nigra pars compacta (SNc) (Anaya-Martinez et al 2006;Gandia et al 1993;Garcia-Cabezas et al 2007Sanchez-Gonzalez et al 2005) and expresses DA receptors (Khan et al 1998;Mrzljak et al 1996).…”

The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons

“…On the basis of its interconnectivity, the RTN is thought to play an important role in attention and information processing (Crick 1984;Steriade et al 1987;Villa et al 1999;Jones 2009;Halassa et al 2011). More recently attention deficit disorder and schizophrenia have also been linked to dysfunction of the RTN (Behrendt 2006;DeLorey et al 2011). In all mammals studied so far, the RTN appears as a thin sheath-like structure of neurons, topographically located between the cortex and dorsal thalamus, which is innervated by excitatory collaterals of the thalamocortical and corticothalamic pathways (Jones 1975).…”

Thalamocortical Pathfinding Defects Precede Degeneration of the Reticular Thalamic Nucleus in Polysialic Acid-Deficient Mice

“…On the one hand, incomplete polysialylation of NCAM during brain development has been proposed as a mechanism for a predisposition to schizophrenia because it causes defects of cortical connectivity, including internal capsule defects, resembling those seen in schizophrenic patients ). On the other hand, dysfunction of the Rt has been linked to schizophrenia (O'Donnell and Grace, 1998;Sharp et al, 2001;Krause et al, 2003;Behrendt and Young, 2004;Behrendt, 2006;Zikopoulos and Barbas, 2007). Since all connections between thalamus and cortex traverse the Rt, this nucleus is ideally positioned to play a role in feedback control of thalamocortical circuits and sensory gating.…”

“…Providing a powerful means for inhibiting thalamocortical activity, the Rt is involved in sensory processing (McAlonan and Brown, 2002;Nagaeva and Akhmadeev, 2006) and, as first hypothesized by Crick (1984), seems to mediate attentional modulation of thalamic neurons (McAlonan et al, 2008). Moreover, dysfunction of the Rt in gating thalamic transmission has been postulated to contribute to the emergence of hallucinations in schizophrenia (Behrendt, 2006;Byne et al, 2009).…”