title: The rostral anterior cingulate cortex modulates the efficiency of amygdala-dependent fear learning.
abstract: BACKGROUND
  The rostral anterior cingulate cortex (rACC) and the amygdala consistently emerge from neuroimaging studies as brain regions crucially involved in normal and abnormal fear processing. To date, however, the role of the rACC specifically during the acquisition of auditory fear conditioning still remains unknown. The aim of this study is to investigate a possible top-down control of a specific rACC sub-region over amygdala activation during pavlovian fear acquisition.
  
  
  METHODS
  We performed excitotoxic lesions, temporal inactivation, and activation of a specific sub-region of the rACC that we identified by tracing studies as supporting most of the connectivity with the basolateral amygdala (r(Amy)-ACC). The effects of these manipulations over amygdala function were investigated with a classical tone-shock associative fear conditioning paradigm in the rat.
  
  
  RESULTS
  Excitotoxic lesions and transient inactivation of the r(Amy)-ACC pre-training selectively produced deficits in the acquisition of the tone-shock associative learning (but not context). This effect was specific for the acquisition phase. However, the deficit was found to be transient and could be overcome by overtraining. Conversely, pre-training transient activation of the r(Amy)-ACC facilitated associative learning and increased fear expression.
  
  
  CONCLUSIONS
  Our results suggest that a subregion of the rACC is key to gating the efficiency of amygdala-dependent auditory fear conditioning learning. Because r(Amy)-ACC inputs were confirmed to be glutamatergic, we propose that recruitment of this brain area might modulate overall basolateral amygdala excitatory tone during conditioned stimulus-unconditioned stimulus concomitant processing. In the light of clinical research, our results provide new insight on the effect of inappropriate rACC recruitment during emotional events.
authors.affiliation: Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bissière
authors.forename: Nicolas
authors.initials: N
authors.lastname: Plachta
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoyer
authors.forename: Kevin H
authors.initials: KH
authors.lastname: McAllister
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Olpe
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Grace
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000161:Acoustic Stimulation; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001245:Association Learning / Q000502:physiology; D001931:Brain Mapping; D003214:Conditioning, Classical / Q000502:physiology*; D003463:Cues; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006179:Gyrus Cinguli / Q000502:physiology*; D009415:Nerve Net / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000502:physiology; D051381:Rats; D011999:Recruitment, Neurophysiological / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid