Parallel Driving and Modulatory Pathways Link the Prefrontal Cortex and Thalamus

Abstract

Pathways linking the thalamus and cortex mediate our daily shifts from states of attention to quiet rest, or sleep, yet little is known about their architecture in high-order neural systems associated with cognition, emotion and action. We provide novel evidence for neurochemical and synaptic specificity of two complementary circuits linking one such system, the prefrontal cortex with the ventral anterior thalamic nucleus in primates. One circuit originated from the neurochemical group of parvalbumin-positive thalamic neurons and projected focally through large terminals to the middle cortical layers, resembling ‘drivers’ in sensory pathways. Parvalbumin thalamic neurons, in turn, were innervated by small ‘modulatory’ type cortical terminals, forming asymmetric (presumed excitatory) synapses at thalamic sites enriched with the specialized metabotropic glutamate receptors. A second circuit had a complementary organization: it originated from the neurochemical group of calbindin-positive thalamic neurons and terminated through small ‘modulatory’ terminals over long distances in the superficial prefrontal layers. Calbindin thalamic neurons, in turn, were innervated by prefrontal axons through small and large terminals that formed asymmetric synapses preferentially at sites with ionotropic glutamate receptors, consistent with a driving pathway. The largely parallel thalamo-cortical pathways terminated among distinct and laminar-specific neurochemical classes of inhibitory neurons that differ markedly in inhibitory control. The balance of activation of these parallel circuits that link a high-order association cortex with the thalamus may allow shifts to different states of consciousness, in processes that are disrupted in psychiatric diseases.

Mapping vulnerability to bipolar disorder: a systematic review and meta-analysis of neuroimaging studies

“…43 Other studies have focused on putative thalamic structural alterations in HR individuals, 31,35,40 as the thalamus plays a key role in cognitive functioning, and prefrontal-thalamic interactions mediate executive functions. 71 However, our metaanalysis found no significant differences between HR individuals and controls in such regions, suggesting that striatal or thalamic structural abnormalities are not trait markers of bipolar disorder.…”

Diversity of Glutamatergic Synaptic Strength in Lateral Prefrontal versus Primary Visual Cortices in the Rhesus Monkey

“…The number of presynaptic vesicles is correlated with neurotransmitter release probability (for review, see Rizzoli and Betz, 2005;Schweizer and Ryan, 2006;Ostroff et al, 2012;Rollenhagen et al, 2014). Moreover, large boutons with more vesicles have been associated with an increased probability of multivesicular release (Tong and Jahr, 1994;Murthy et al, 1997;Prange and Murphy, 1999), which, if asynchronous, could contribute to the higher frequency of mEPSCs seen in LPFC.…”

“…Germuska et al, 2006;Zikopoulos and Barbas, 2007), which is in turn correlated with the probability of neurotransmitter release during synaptic events (Tong and Jahr, 1994;Murthy et al, 1997Schikorski and Stevens, 2001;Li et al, 2005). Here we measured the two-dimensional outer diameters of vesicles and counted the mean number of vesicles per bouton from a series of high-magnification EM images of LPFC versus V1 neuropil.…”

Functional Outcome in People at High Risk for Psychosis Predicted by Thalamic Glutamate Levels and Prefronto-Striatal Activation

“…41 However, the data from this study cannot determine whether there is a causal relationship between alterations in thalamic glutamate levels and prefrontal activation. Nevertheless, PFCthalamic interactions mediate attentional and executive functions 41,42 via direct connections from the thalamus to the PFC that loop back to the thalamus via the striatum and globus palidus. 43 Moreover, a recent study describes reduced PFC-thalamic connectivity in schizophrenia.…”