Altered Basolateral Amygdala Encoding in an Animal Model of Schizophrenia

Abstract

It has been proposed that schizophrenia results, in part, from the inappropriate or spurious attribution of salience to cues in the environment. We have recently reported neural correlates of salience in the basolateral amygdala (ABL) of rats during learning in an odor-guided discrimination task. Here we tested whether this dopamine-dependent salience signal is altered in rats with neonatal ventral hippocampal lesions (NVHLs), a rodent model of schizophrenia. We found that ABL signals related to violations in reward prediction were only mildly affected by NVHL; however, neurons in rats with NVHLs showed significantly stronger selectivity during odor sampling, particularly for the more salient large-reward cue. The elevated cue-evoked activity in NVHL rats was correlated with heightened orienting behavior and also with changes in firing to the shifts in reward, suggesting that it reflected abnormal signaling of the large rewardpredicting cue's salience. These results are broadly consistent with the proposal that schizophrenics suffer from enhanced signaling of salience.

General and emotion-specific neural effects of ketamine during emotional memory formation

“…The salience processing networks, particularly the amygdala and to a lesser extend the orbitofrontal cortex, have been proposed to show hyper-reactivity during psychotic states at early stages of schizophrenia as a consequence of reduced cortico-accumbens glutamate activity that in turn fails to provide a tonic dopaminergic down-regulation of the phasic dopamine system leading to an exaggerated response to potentially significant stimuli (Grace et al, 2000;Aleman and Kahn, 2005). The role of dopamine in gating amygdala responsivity is further supported by findings on positive associations between measures of amygdala dopamine and higher functional activity in response to aversive stimuli in healthy individuals (Kienast et al, 2008) as well as recent animal models of schizophrenia that revealed disrupted, particularly exaggerated amygdala, dopamine salience signaling that have been proposed to underlie enhanced salience signaling in schizophrenia patients (Hernandez et al, 2015).…”

Amygdalar and Hippocampal Morphometry Abnormalities in First-Episode Schizophrenia Using Deformation-Based Shape Analysis

“…The observed FES-related amygdalar atrophies were found to concentrate on the basolateral and centromedial subregions. Studies have already shown that the basolateral amygdala plays a key role in the abnormal behavior of schizophrenia (48). The reasons are potentially two-fold: firstly, one of the most important brain regions in schizophrenia, the prefrontal cortex, receives heavy inputs from the basolateral amygdala.…”

Neurophysiology of Reward-Guided Behavior: Correlates Related to Predictions, Value, Motivation, Errors, Attention, and Action

“…Understanding how these circuits work to produce behavior allows us to look for alterations in neural signals in animal models of human disorders, such as models of psychological disorders, drug addiction, and aging (Hernandez et al 2015; Roesch et al 2007b, 2012a, b; Gruber et al 2010; Stalnaker et al 2009). Future therapeutic methods (behavioral, psychological, pharmacological, etc.)…”