Temporal Encoding in Fear Conditioning Revealed Through Associative Reflex Facilitation.

Abstract

Temporal encoding in Pavlovian fear conditioning was examined through conditional facilitation of the short-latency (Rl) component of the rat eyeblink reflex. Rats were fear-conditioned to a tone conditional stimulus (CS) with either a 3- or 9-s interstimulus interval (ISI) between CS onset and the onset of the grid-shock unconditional stimulus (US). Rl facilitation was tested over 2 days, in counterbalanced order, at a latency of 3 s and 9 s from CS onset. CS-produced Rl facilitation, the conditional response (CR), was 3-4 times larger when the test latency equaled the conditioning ISI. These results, coupled with the known neurophysiology of Rl facilitation, suggest that this CR could disclose differences in the time course of CS-generated output from the amygdala when driven by cortical versus subcortical CS-CR pathways.

Auditory Cortex Is Required for Fear Potentiation of Gap Detection

“…This indicates that auditory cortex is critically involved in associative learning of the emotional significance of temporally structured sounds. Auditory cortex is not required for fear conditioning when using a pure tone or white noise CS (LeDoux et al, 1984, LeDoux et al, 1986a, LeDoux et al, 1986b, Romanski and LeDoux, 1992, Campeau and Davis, 1995, but is required with more complex stimuli such as frequency-modulated sweeps (Letzkus et al, 2011). It is still not clear which aspects of stimulus complexity predict the necessity of auditory cortex for fear conditioning (Lindquist andBrown, 2004, Kholodar-Smith et al, 2008).…”

“…First, we measured behavior in offspring (n ϭ 66) of a cross between a CaMKII-tTA line ("CaMKII," 003010; The Jackson Laboratory) and a tTA-dependent Archaerhodopsin (Arch) line (Weible et al, 2014). In these mice, Arch (Han et al, 2011) was expressed in CaMKII ϩ pyramidal neurons. Second, we assessed behavior in homozygotic offspring (n ϭ 72) of a cross between Pvalb-IRES-Cre ("PV," 008069; The Jackson Laboratory) and CAG-ChR2-eYFP (012569; The Jackson Laboratory) lines.…”

“…Auditory cortex is required for the detection of brief (10 ms) gaps (Ison et al, 1991, Threlkeld et al, 2008, Weible et al, 2014 and, A B C D Figure 5. Optogenetic activation of PV ϩ interneurons suppressed sound-evoked activity throughout auditory cortex and significantly reduced behavioral gap detection and neuronal GTRs.…”

“…Gap detection is a model for the encoding and processing of temporal structure, in which animals detect the presence of a gap in ongoing background noise. These gaps mimic voice-onset time and similar gaps within and between phonemes, which are critical cues for segmentation and discrimination of speech sounds (Lisker and Abramson, 1964, Brugge and Merzenich, 1973, Eggermont, 1999, Phillips et al, 2002, Engineer et al, 2008. Recent work in rats and mice has shown that auditory cortex is necessary for detection of brief gaps (Ͻ50 ms), but not longer gaps (Ison et al, 1991, Threlkeld et al, 2008, Weible et al, 2014.…”

“…These gaps mimic voice-onset time and similar gaps within and between phonemes, which are critical cues for segmentation and discrimination of speech sounds (Lisker and Abramson, 1964, Brugge and Merzenich, 1973, Eggermont, 1999, Phillips et al, 2002, Engineer et al, 2008. Recent work in rats and mice has shown that auditory cortex is necessary for detection of brief gaps (Ͻ50 ms), but not longer gaps (Ison et al, 1991, Threlkeld et al, 2008, Weible et al, 2014. However, auditory cortex is not necessary for many other auditory tasks, such as prepulse inhibition (PPI) of startle responses, frequency discrimination, or fear conditioning to pure tone stimuli (Ohl et al, 1999, LeDoux, 2000, Swerdlow et al, 2001.…”