LTD at amygdalocortical synapses as a novel mechanism for hedonic learning

Abstract

207 words; Abstract Sensory stimuli are perceived and processed according to their physicochemical and affective signatures. For example, taste perception depends on the chemical identity of a tastant, as well as on its pleasantness or aversiveness. The affective value of a palatable gustatory stimulus changes if it becomes associated with gastric malaise, a phenomenon known as conditioned taste aversion (CTA) 1 . CTA depends on activity in the gustatory portion of the insular cortex (GC) and in the basolateral nucleus of the amygdala (BLA) 2,3 . Indeed, inactivation of GC or BLA impairs CTA 4-8 . Signaling mechanisms typically associated with induction of long term synaptic plasticity are engaged in this form of learning 9,10 , suggesting that the shift in perception from pleasant to aversive depends on changes in synaptic efficacy. Here we report that CTA modulates synaptic drive onto GC pyramidal neurons, and that long term synaptic depression (LTD) at BLA -GC inputs is sufficient to change the hedonic value of a taste stimulus. Our results demonstrate a direct role for amygdalocortical LTD in taste aversion learning.A novel, pleasant taste stimulus becomes aversive if associated with gastric malaise 1 . This effect is common to vertebrates and invertebrates and is an important survival response, as eating the wrong food may be deadly. In rodents, CTA can be induced by association of a sucrose solution

Intrinsic excitability in layer IV-VI anterior insula to basolateral amygdala projection neurons encodes the confidence of taste valence

“…We have previously shown that compared to CTA retrieval and reinstatement, appetitive memory retrieval and extinction were associated with (a) an enhancement of IEG induction (c-fos and Npas4) at the aIC, and (b) decreased frequency of pre-synaptic inhibition on the aIC-BLA (Yiannakas et al, 2021). In accord, other published work investigating the induction of IEG in the rodent IC, found that consistent with a reduction in spiking activity (Grossman et al, 2008), the induction of c-fos at the IC was suppressed by aversive taste memory retrieval (Haley et al, 2020). Earlier studies have also reported increases in c-fos following the extinction of cyclosporine A-induced CTA (Hadamitzky et al, 2015).…”

“…Guided by evidence regarding the induction of plasticity cascades, the expression of immediate early genes, as well as the timeframes involved in LTP and LTD at the IC (Rosenblum et al, 1997;Hanamori et al, 1998;Jones et al, 1999;Escobar and Bermúdez-Rattoni, 2000), the five treatment groups were sacrificed 1 hour following taste consumption. Even though changes in activity can be observed within seconds to minutes, depending on their novelty, salience and valence (Barot et al, 2008;Lavi et al, 2018;Wu et al, 2020), sensory experiences can modulate the function of IC neurons for hours (Juárez-Muñoz et al, 2017;Rodríguez-Durán et al, 2017;Haley et al, 2020;Yiannakas et al, 2021).We had previously identified a CaMKII-dependent short-term memory trace at the IC that last for the first 3 hours following taste experiences, regardless of their valence (Adaikkan and Rosenblum, 2015). To address whether similar time-dependency of the physiological correlations engaged by the IC during novel taste learning, a 6 th group was sacrificed 4 hours following novel saccharin exposure (Figure 1 -Saccharin 1x (4hrs)).…”

Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion

“…We found that strong CTA conditioning produced a significant increase in mEPSC amplitude in RAM + neurons; more surprisingly, a similar increase was observed in RAM - neurons when compared to neurons recorded from moderate CTA animals ( Figure 3D & 3E ). Other studies have similarly documented changes in synaptic strength in GC neurons using whole-cell physiology following CTA learning without an activity-dependent labeling scheme, suggesting that synaptic plasticity occurs across a large population of cells in GC (Haley et al, 2020). These findings reveal that strong CTA conditioning produces a long-lasting increase in postsynaptic strengths that parallels the long-lasting generalized aversion and suggest a possible GC-wide induction of synaptic plasticity.…”

“…CTA conditioning is known to induce dynamic changes in firing rate within GC, which may suggest that different neuronal populations may undergo changes in synaptic plasticity on distinct time scales post-conditioning and this temporal activation facilitates the formation of an aversive memory (Moran & Katz, 2014; Arieli, Younis, & Moran, 2021). Additionally, previous studies have documented changes in synaptic strength in GC neurons following CTA training without an activity dependent labeling scheme, suggesting that synaptic plasticity occurs across a large population of cells in GC (Haley et al, 2020). Taken together, these findings hint at the possibility of GC-wide induction of synaptic plasticity following CTA conditioning.…”

Brain Signaling of Indispensable Amino Acid Deficiency

“…Here, muscarinic receptor antagonists blocked the CTA. The synaptic connections between the BLA and the insular cortex were described by Haley et al [65], and cFos expression has been seen by several observers in the BLA and insular cortex after hours of CTA exposure reviewed in [53]. Further interactions between these brain areas include the observation that brain-derived neurotrophic factor (BDNF) increased signaling capabilities of the insular cortex, and changing the duration of the CTA [66].…”