Molecular correlates of separate components of training that contribute to long-term memory formation after learning that food is inedible in Aplysia

Abstract

Training with inedible food for a period that is too brief to produce long-term memory becomes effective in producing memory when training is paired with a nitric oxide (NO) donor. Lip stimulation for the same period of time paired with an NO donor is ineffective. Using qPCR, we examined molecular correlates of brief training versus lip stimulation, of treatment with an NO donor versus saline, and of the combined stimuli producing long-term memory. Changes were examined in mRNA expression of homologs of ,, ,, and , in both the buccal and cerebral ganglia controlling feeding. Both the brief training and the NO donor increased expression of, ,, and , but not in the buccal ganglia. For , there was a significant interaction between the effects of the brief training and of the NO donor. In addition, the NO donor, but not brief training, increased expression of all of the genes in the cerebral ganglion. These findings show that the components of learning that alone do not produce memory produce molecular changes in different ganglia. Thus, long-term memory is likely to arise by both additive and interactive increases in gene expression.

NO is required for memory formation and expression of memory, and for minor behavioral changes during training with inedible food in Aplysia

“…A number of previous reports have localized molecular correlates of memory formation to the buccal ganglia (Levitan et al 2008(Levitan et al , 2012Briskin-Luchinsky et al 2018), whereas we propose above that the effects of NO during training occur in the cerebral ganglion. It is possible that different aspects of memory are stored in different ganglia.…”

“…4). In addition, a previous study found that injecting behaving animals with an NO donor, which substitutes for attempts to swallow, causes increased expression of genes associated with memory consolidation, such as CREB1 and C/EBP, in the cerebral ganglion (Briskin-Luchinsky et al 2018).…”

“…In addition, exogenous NO paired with lip stimulation that is continued for the full length of a training session produces long-term memory 24 h after the training (Katzoff et al 2006(Katzoff et al , 2010. A later study showed that pairing exogenous NO with even a 3 min training in which animals attempt to swallow food can produce 24 h memory (Briskin-Luchinsky et al 2018). In the absence of exogenous NO, a 3 min training is generally too short to produce memory because of too few attempts to swallow the food.…”

Successful and unsuccessful attempts to swallow in a reduced Aplysia preparation regulate feeding responses and produce memory at different neural sites

“…However, changes in molecular correlates measured in the whole cerebral ganglia would not pick up changes localized to a small number of key neurons, such as the cholinoceptive command-like CBI neurons, leaving open the possibility that changes in the response to ACh may also underlie aspects of long-term memory. Previous reports (Briskin-Luchinsky et al 2018a) also found that treatment with an NO donor produces changes in the cerebral ganglion, and the NO donor applied to the cerebral ganglion inhibits CCh-induced motor programs (Briskin-Luchinsky et al 2018b), suggesting that the effects of NO on memory formation are localized to the cerebral ganglion.…”

“…Previous studies on molecular correlates of long-term memory formation showed increases after training in the buccal ganglia, but no changes in expression were found in the whole cerebral ganglion (Levitan et al 2008;Michel et al 2011;Briskin-Luchinsky et al 2018a). However, changes in molecular correlates measured in the whole cerebral ganglia would not pick up changes localized to a small number of key neurons, such as the cholinoceptive command-like CBI neurons, leaving open the possibility that changes in the response to ACh may also underlie aspects of long-term memory.…”