Opposing Roles of Cholinergic and GABAergic Activity in the Insular Cortex and Nucleus Basalis Magnocellularis during Novel Recognition and Familiar Taste Memory Retrieval

Abstract

Acetylcholine (ACh) is thought to facilitate cortical plasticity during memory formation and its release is regulated by the nucleus basalis magnocellularis (NBM). Questions remain regarding which neuronal circuits and neurotransmitters trigger activation or suppression of cortical cholinergic activity. During novel, but not familiar, taste consumption, there is a significant increase in ACh release in the insular cortex (IC), a highly relevant structure for taste learning. Here, we evaluate how GABA inhibition modulates cholinergic transmission and its involvement during taste novelty processing and familiar taste memory retrieval. Using saccharin as a taste stimulus in a taste preference paradigm, we examined the effects of injecting the GABAA receptor agonist muscimol or the GABAA receptor antagonist bicuculline into the IC or NBM during learning or retrieval of an appetitive taste memory on taste preference in male Sprague Dawley rats. GABAA receptor agonism and antagonism had opposite effects on cortical ACh levels in novel taste presentation versus familiar taste recognition and ACh levels were associated with the propensity to acquire or retrieve a taste memory. These results indicate that the pattern of cortical cholinergic and GABAergic neuroactivity during novel taste exposure is the opposite of that which occurs during familiar taste recognition and these differing neurotransmitter system states may enable different behavioral consequences. Divergences in ACh and GABA levels may produce differential alterations in excitatory and inhibitory neural processes within the cortex during acquisition and retrieval.

Significance statement: During learning and recall, several brain structures act together. This work demonstrates interactions between cortical cholinergic and GABAergic systems during taste learning and memory retrieval. We found that the neuroactivity pattern during novel taste exposure is opposite that which occurs during familiar taste recognition. GABAA receptors must be inactive during novel tasting to enable new memory formation, but must be active and inhibiting acetylcholine release in the cortex to allow memory retrieval. These findings indicate that GABA inhibition modulates cholinergic transmission and that cholinergic-GABAergic system interactions are important during the transition from novel to familiar memory.

Keywords: GABA receptors; appetitive; microdialysis; pharmacology; taste preference.

Figure 1.

Coronal section diagrams and representative photomicrographs of cannulae and probe placement in the IC and NBM. A, Groups with one stainless steel cannula in the left IC and one dual probe (injector and microdialysis probe) in the right IC. B, Groups with bilateral NBM injection cannulae and one cannula/microdialysis probe in the right IC. Arrows (above) and dots (below) show locations of stainless steel cannulae. Lines show microdialysis probes (modified from Paxinos and Watson, 1998).

Figure 2.

Microdialysis in freely moving rats. A total of 13/15 min samples were collected from the right IC during novel or familiar taste presentation. The black arrow indicates drug injection and the black bar saccharin presentation

Figure 3.

Taste preference effects of bilateral intra-IC injections and intra-NBM injections of muscimol and bicuculline. Consumption of saccharin as a novel tastant (A: saline, n = 11; muscimol, n = 10; bicuculline, n = 11) and (C: saline, n = 12; muscimol, n = 12; bicuculline, n = 12). Consumption of saccharin as a familiar tastant (memory retrieval) (B: saline, n = 12; muscimol, n = 12; bicuculline, n = 13) and (D: saline, n = 10; muscimol, n = 11; bicuculline, n = 11). Data are shown as the percentage saccharin consumption ± SEM, *p < 0.05, **p < 0.001 versus control. Arrows indicate injection day.

Figure 4.

Extracellular ACh levels in the IC during novel taste presentation and IC injections (A) and familiar taste presentation in groups that received IC injections 24 h earlier (B) (saline, n = 5; muscimol, n = 6). Novel taste presentation and NBM injections (C) and familiar taste presentation in groups that received NBM injections 24 h earlier (D) (saline, n = 6; muscimol, n = 5). Black arrow indicates IC saline or muscimol injection and the black bar indicates saccharin presentation. Independent groups in A–D: *p < 0.05, **p < 0.001 versus control. Inset, Percentage saccharin consumption of each group during the microdialysis procedure.

Figure 5.

Extracellular ACh levels in the IC during novel taste presentation and IC injections and novel taste presentation (A) and familiar taste presentation in groups that received IC injections 24 h earlier (B) (saline, n = 5; bicuculline, n = 5). C, D, Novel taste presentation and NBM injections (C) and familiar taste presentation in groups that received NBM injections 24 h earlier (D) (saline, n = 5; bicuculline, n = 6). Black arrow indicates IC saline or bicuculline injection and black bar indicates saccharin presentation. Independent groups in A–D: *p < 0.05, **p < 0.001 versus control. Inset, Percentage saccharin consumption during the microdialysis procedure.

Figure 6.

Extracellular GABA levels in the IC during novel and familiar saccharin taste presentation (novel, n = 5; familiar, n = 5). Black bar indicates saccharin presentation (*p < 0.05 vs control). Inset, Percentage saccharin consumption of each group during the microdialysis procedure. BL, Baseline.