A role for midline and intralaminar thalamus in the associative blocking of Pavlovian fear conditioning

Abstract

Fear learning occurs in response to positive prediction error, when the expected outcome of a conditioning trial exceeds that predicted by the conditioned stimuli present. This role for error in Pavlovian association formation is best exemplified by the phenomenon of associative blocking, whereby prior fear conditioning of conditioned stimulus (CS) A is able to prevent learning to CSB when they are conditioned in compound. The midline and intralaminar thalamic nuclei (MIT) are well-placed to contribute to fear prediction error because they receive extensive projections from the midbrain periaqueductal gray—which has a key role in fear prediction error—and project extensively to prefrontal cortex and amygdala. Here we used an associative blocking design to study the role of MIT in fear learning. In Stage I rats were trained to fear CSA via pairings with shock. In Stage II rats received compound fear conditioning of CSAB paired with shock. On test, rats that received Stage I training expressed less fear to CSB relative to control rats that did not receive this training. Microinjection of bupivacaine into MIT prior to Stage II training had no effect on the expression of fear during Stage II and had no effect on fear learning in controls, but prevented associative blocking and so enabled fear learning to CSB. These results show an important role for MIT in predictive fear learning and are discussed with reference to previous findings implicating the midline and posterior intralaminar thalamus in fear learning and fear responding.

The ventrolateral periaqueductal grey updates fear via positive prediction error

“…So while clues to the neuron type identity can be found, further work is necessary. As for the target(s) of the vlPAG +PE, the midline/intralaminar thalamus has been offered (McNally et al., ; Sengupta & McNally, ). The vlPAG projects to a host of brain regions implicated in prediction and prediction error, including the major dopamine‐containing regions (A8 retrorubral field, A9 substantia nigra and A10 ventral tegmental area) (Watabe‐Uchida, Zhu, Ogawa, Vamanrao, & Uchida, ), the diagonal band and the lateral bed nucleus of the stria terminalis (Beitz, ).…”

Limbic thalamus and state-dependent behavior: The paraventricular nucleus of the thalamic midline as a node in circadian timing and sleep/wake-regulatory networks

“…Hamlin et al, 2009;Price and Drevets, 2010;Saalmann, 2014;Sengupta and McNally, 2014;Varela, 2014). This may seem surprising given that the midline nuclei, together with the intralaminar nuclei, have historically represented the core of the "nonspecific thalamus", involved in a general role of diffuse activation of the cortical mantle.…”

“…Benarroch, 2008;Sengupta and McNally, 2014;Van der Werf et al, 2002;Varela, 2014). It remains that these cell groups differ from sensory and motor relay nuclei of the dorsal thalamus in their effect on sleep and arousal, function in cognitive tasks, mechanisms of temporal synchronization and temporal binding in the cerebral cortex (e.g.…”

“…On the other hand, the dorsal thalamic midline, whose main component is the paraventricular nucleus of the thalamus (PVT), has been implicated in the response to psychoactive drugs (Cohen et al, 1998;Deutch et al, 1995Deutch et al, , 1998, adaptation to stressful conditions, modulation of viscerosensory stimuli, positive and negative emotional states, drug-seeking and reward mechanisms (e.g. James and Dayas, 2013;Martin-Fardon and Boutrel, 2012;Hsu et al, 2014;Sengupta and McNally, 2014).…”

Adaptive disinhibitory gating by VIP interneurons permits associative learning

“…To this end, we injected a cre-dependent AAV encoding the TVA receptor and rabies glycoprotein unilaterally into the BLA of VIP-cre, PV-cre or SOM-cre mice, followed by the injection of rabiesG two weeks later (Figures 2A and S2). VIP interneurons received major inputs from auditory areas in cortex and thalamus, as well as from brain regions involved in aversive signaling such as the dorsal midline and intralaminar thalamus as well as the insular cortex (Lanuza et al, 2008;2004;Sengupta and McNally, 2014) (Figures 2B-F and S3A-B). We further observed strong rabies labeling in the basal forebrain, which in part comprised cholinergic basal forebrain neurons (Figures 2C and S3C).…”