Brain region-specific activity patterns after recent or remote memory retrieval of auditory conditioned fear

Abstract

Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or retrieval. To investigate this possibility, we systematically imaged the brain activity patterns in the lateral amygdala, MGm/PIN, and AuV/TeA using activity-dependent induction of immediate early gene zif268 after recent and remote memory retrieval of auditory conditioned fear. Consistent with the critical role of the amygdala in fear memory, the zif268 activity in the lateral amygdala was significantly increased after both recent and remote memory retrieval. Interesting, however, the density of zif268 (+) neurons in both MGm/PIN and AuV/TeA, particularly in layers IV and VI, was increased only after remote but not recent fear memory retrieval compared to control groups. Further analysis of zif268 signals in AuV/TeA revealed that conditioned tone induced stronger zif268 induction compared to familiar tone in each individual zif268 (+) neuron after recent memory retrieval. Taken together, our results support that the lateral amygdala is a key brain site for permanent fear memory storage and suggest that MGm/PIN and AuV/TeA might play a role for remote memory storage or retrieval of auditory conditioned fear, or, alternatively, that these auditory brain regions might have a different way of processing for familiar or conditioned tone information at recent and remote time phases.

Region- and Layer-Specific Activation of the Higher Order Auditory Cortex Te2 after Remote Retrieval of Fear or Appetitive Memories

“…At variance with our study, however, Kwon et al (Kwon et al 2012) reported that auditory fear memory retrieval did not modify zif268 signals in higher order auditory cortex in mice. The authors suggest that the difference between their study and our previous data (Sacco and Sacchetti 2010) "might result from different behavioral protocols used in each study and probably reflect species differences in functional neural circuit organization in the mouse and rat brains" (Kwon et al 2012). However, several previous studies have reported memory-related plasticity in laminae II/III in both rats and mice.…”

“…Concerning thalamic projections, Te2 cortex receives projections from the medial and the dorsal division of the geniculate body (Antunes and Moita 2010;Arnault and Roger 1990;Kolb and Tees 1990). Several studies have indicated that these thalamic nuclei are involved in fear learning processes (Antunes and Moita 2010;Apergis-Schoute et al 2005;Han et al 2008;Weinberger 20 2011) and in remote fear memory storage/retrieval (Kwon et al 2012). The enhanced zif268 staining detected in layer IV may therefore reflect the activity of such thalamic-to-cortical connectivity during fear memory processes.…”

“…This concept is in line with previous results showing that the Te2 is not significantly activated by non-associative auditory processes, such as long-term habituation to neutral sounds (Gonzalez-Lima and Scheich 1985;Gonzales-Lima et al 1989) and that lesions in the higher order sensory cortices did not destroy the long-term ability to recognize the physical features of the perceived stimuli (Sacco and Sacchetti 2010). Accordingly, novel and familiar sounds activate Te2 neurons in a similar manner in the absence of conditioning (Sacco and Sacchetti 2010;Wan et al 2001), while neural activity in this area increases significantly if the sounds had previously acquired a behavioral value (Cambiaghi et al 2016;Carretta et al 1999;Kwon et al 2012;Grosso et al 2015b;Sacco and Sacchetti 2010). Similar results were reported by Bao et al (Bao et al 2001), who showed that, after pairing of auditory stimuli presentation to ventral tegmental area stimulation, "strong, sharply tuned responses to the paired tones also emerge in a second cortical area [Te2], whereas the same stimuli only evoke 23 poor or non-selective responses in this second cortical field in naive animals."…”

“…Accordingly, several recent studies have shown changes in zif268 expression in the sensory cortex following emotional memory processes (Hall et al 2001;Kwon et al 2012;Maviel et al 2004;Sacco and Sacchetti 2010). Then, we investigated how Te2 activity was shaped by presenting identical tones that had been previously paired to appetitive stimuli.…”

Optogenetic activation of presynaptic inputs in lateral amygdala forms associative fear memory

“…However, changes in response to fear learning have also been found in other subcortical and cortical regions (Fanselow and Poulos 2005;Letzkus et al 2011;Gdalyahu et al 2012). In particular, the thalamic and cortical auditory regions upstream of the LA show increased neuronal activity and synaptic changes in response to the CS (Gerren and Weinberger 1983;Weinberger 1998;Cahill et al 1999;Kwon et al 2012), suggesting that plasticity at these auditory afferents might be necessary to form associative fear memory, rather than to simply deliver sensory information (Parsons et al 2006).…”