Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 50 (7), 3141-3163

β-Adrenergic Modulation of Discrimination Learning and Memory in the Auditory Cortex

Affiliations

β-Adrenergic Modulation of Discrimination Learning and Memory in the Auditory Cortex

Horst Schicknick et al. Eur J Neurosci.

Abstract

Despite vast literature on catecholaminergic neuromodulation of auditory cortex functioning in general, knowledge about its role for long-term memory formation is scarce. Our previous pharmacological studies on cortex-dependent frequency-modulated tone-sweep discrimination learning of Mongolian gerbils showed that auditory-cortical D1/5 -dopamine receptor activity facilitates memory consolidation and anterograde memory formation. Considering overlapping functions of D1/5 -dopamine receptors and β-adrenoceptors, we hypothesised a role of β-adrenergic signalling in the auditory cortex for sweep discrimination learning and memory. Supporting this hypothesis, the β1/2 -adrenoceptor antagonist propranolol bilaterally applied to the gerbil auditory cortex after task acquisition prevented the discrimination increment that was normally monitored 1 day later. The increment in the total number of hurdle crossings performed in response to the sweeps per se was normal. Propranolol infusion after the seventh training session suppressed the previously established sweep discrimination. The suppressive effect required antagonist injection in a narrow post-session time window. When applied to the auditory cortex 1 day before initial conditioning, β1 -adrenoceptor-antagonising and β1 -adrenoceptor-stimulating agents retarded and facilitated, respectively, sweep discrimination learning, whereas β2 -selective drugs were ineffective. In contrast, single-sweep detection learning was normal after propranolol infusion. By immunohistochemistry, β1 - and β2 -adrenoceptors were identified on the neuropil and somata of pyramidal and non-pyramidal neurons of the gerbil auditory cortex. The present findings suggest that β-adrenergic signalling in the auditory cortex has task-related importance for discrimination learning of complex sounds: as previously shown for D1/5 -dopamine receptor signalling, β-adrenoceptor activity supports long-term memory consolidation and reconsolidation; additionally, tonic input through β1 -adrenoceptors may control mechanisms permissive for memory acquisition.

Keywords: ICI118,551; Mongolian gerbil; acquisition; atenolol; clenbuterol; consolidation; isoproterenol; propranolol; reconsolidation; xamoterol.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Post‐acquisition propranolol application caused a discrimination deficit in session 2. Data were collected in Experiment 1. Gerbils were trained on the FM discrimination (1–2 kHz vs. 2–1 kHz) for 3 sessions. Injections of vehicle (Veh, = 15) or 33.8 mM propranolol (Pro, = 15) were applied to the auditory cortex twice, that is, immediately after and 2 hr after completion of session 1. (a) Discrimination rates per training session, that is, the differences between the relative frequencies of correct conditioned responses (CR+) and false alarms (CR‐) per training session, are referred to as D session [%] in the y‐axis label (group means ± SEM). (b–d) Each of sessions 1 and 2 was subdivided into 5 blocks of 12 trials (cf. Figure S2A). (b) Discrimination rates per trial block, that is, the differences between the relative frequencies of CR+ and CR‐ per trial block, are referred to as D block [%] in the y‐axis label (group means ± SEM). (c1–2) Relative frequencies of CR+ (filled bars) and CR‐ (empty bars) per trial block are referred to as CR block [%] in the y‐axis label for the Veh (c1) and Pro (c2) group (individual data points and group means + SEM). (d) Total frequencies of hurdle crossings per trial block, that is, the sums of the relative frequencies of CR+ and CR‐ per trial block, are referred to as ∑CR block [%] in the y‐axis label (group means ± SEM). Arrows indicate the approximate injection times. ***< 0.005, significant group difference (a: t test; b: RMANOVA). # < 0.05, ## < 0.01, ### < 0.005, significantly different from the corresponding CR‐ rate (t test)
Figure 2
Figure 2
Immediate but not delayed propranolol application after the 7th training session suppressed the previously established FM discrimination. Data were collected in Experiments 2 (a, b; = 6) and 3 (c, d; = 3). Gerbils were trained on the FM discrimination for 10 sessions. Surgical operation (OP) was performed after session 6. Propranolol (33.8 mM) was applied to the auditory cortex twice, that is, immediately and 2 hr (a, b) or 2 and 4 hr (c, d) after completion of session 7. (a, c) Discrimination rates per training session (group means ± SEM). (b, d) Relative frequencies of correct conditioned responses (CR+) and false alarms (CR‐) per session for training sessions 6–10 (individual data points and group means + SEM). Arrows indicate the approximate injection times. $$ < 0.01, significant session effect (RMANOVA). § < 0.05, §§§ < 0.005, significantly different from the value in session 7 (t test). # < 0.05, ## < 0.01, ### < 0.005, significantly different from the corresponding CR‐ rate (t test). Note, gerbils that received propranolol immediately after session 7 failed to discriminate between CS+ and CS‐ in session 8 (b)
Figure 3
Figure 3
Inhibition of auditory‐cortical β‐adrenoceptors 1 day before conditioning impaired FM discrimination learning. Data were collected in Experiment 4. Gerbils were trained on the FM discrimination for three sessions. Vehicle (Veh, = 8), 33.8 mM propranolol (Pro, = 3) or a mixture (Mix, = 6) containing 3.8 mM atenolol and 0.32 μM ICI118,551 was applied to the auditory cortex twice, that is, 24 and 22 hr prior to the beginning of session 1. (a) Discrimination rates per training session expressed as group means ± SEM; arrows indicate the approximate injection times. (b1–3) Relative frequencies of correct conditioned responses (CR+) and false alarms (CR‐) per session for gerbils of the Veh (b1), Pro (b2) and Mix group (b3) are shown as individual data points and group means + SEM. ***< 0.005, significant treatment effect (RMANOVA). *< 0.05, significantly different from Veh (Dunnett's test). # < 0.05, ### < 0.005, significantly different from the corresponding CR‐ rate (t test). Note, both groups of antagonist‐treated gerbils failed to discriminate between CS+ and CS‐
Figure 4
Figure 4
Extended training enabled FM discrimination learning after propranolol treatment. Data were collected in Experiment 5. Gerbils were trained on the FM discrimination for five sessions. Vehicle (Veh, = 5) or 33.8 mM propranolol (Pro, = 6) was applied to the auditory cortex twice, that is, 24 and 22 hr prior to the start of session 1. (a) Discrimination rates per training session expressed as group means ± SEM; arrows indicate the approximate injection times. (b1–2) Relative frequencies of correct conditioned responses (CR+) and false alarms (CR‐) per session for gerbils of the Veh (b1) and Pro‐group (b2) are shown as individual data points and group means + SEM. ***< 0.005, significant treatment effect (RMANOVA). # < 0.05, ## < 0.01, significantly different from the corresponding CR‐ rate (t test). Note, the Pro‐group achieved a significant difference between the rates of CR+ and CR‐ in session 5
Figure 5
Figure 5
Subtype‐selective β1‐adrenoceptor inhibition 1 day before initial conditioning impaired FM discrimination learning. Data were collected in Experiment 6. Gerbils were trained on the FM discrimination for five sessions. Vehicle (Veh, = 9), 3.8 mM atenolol (Ate, = 6) or 0.32 μM ICI118,551 (ICI,= 3) was applied to the auditory cortex twice, that is, 24 and 22 hr prior to the start of session 1. Discrimination rates per training session are shown as group means ± SEM. Arrows indicate the approximate injection times. **< 0.01, significant treatment x session interaction (RMANOVA). *< 0.05, significantly different from Veh (Dunnett's test)
Figure 6
Figure 6
Subtype‐selective β1‐adrenoceptor stimulation 1 day before initial conditioning improved FM discrimination learning. Data were collected in Experiment 7. Gerbils were trained on the FM discrimination for three sessions. Vehicle (Veh, = 10), 2.8 mM isoproterenol (Iso, = 6), 10 mM xamoterol (Xam, = 3) or 0.32 mM clenbuterol (Cle, = 3) was applied to the auditory cortex twice, that is, 24 and  22 hr prior to the start of session 1. (a) Discrimination rates per session are shown for training sessions 1–3 as group means ± SEM; arrows indicate the approximate injection times. (b) Discrimination rates per session are shown in detail for training session 1 (individual data points and group means + SEM). (c1–2) Relative frequencies of correct conditioned responses (CR+) and false alarms (CR‐) in training session 1 are shown, calculated as an average per session (c1; individual data points and group means + SEM) and per trial block (c2; group means + SEM). *< 0.05, significant group difference (Fisher's PLSD). # < 0.05, ## < 0.01, significant difference between the rates of CR+ and CR‐ (t test)
Figure 7
Figure 7
FM detection learning was not affected after auditory‐cortical propranolol infusion. Data were collected in Experiment 8. Gerbils were trained on the two‐way active avoidance task for five sessions to detect a single FM (1–2 kHz). Vehicle (Veh, = 6) or 33.8 mM propranolol (Pro, = 6) was applied to the auditory cortex twice, that is, 24 and 22 hr prior to the start of session 1. Avoidance rates per training session are shown. Arrows indicate the approximate injection times. All data points represent group means ± SEM
Figure 8
Figure 8
β1‐ and β2‐adrenergic receptors are abundant in the auditory cortex of the Mongolian gerbil. They can be found widely distributed within the neuropil and at the somata of pyramidal (layers IIIII and V‐VI) and non‐pyramidal neurons (mainly layer IV). [Colour figure can be viewed at http://wileyonlinelibrary.com]
Figure 9
Figure 9
Various effects of β‐adrenergic modulation of FM discrimination learning and memory in the auditory cortex. Based on our data, we propose a hypothetical model for β‐adrenoceptor signalling during processes of memory formation, consolidation and reconsolidation. First, in naive animals, that is, without explicit task engagement, β1‐adrenoceptor activity promotes mechanisms that facilitate subsequent FM discrimination (not detection) learning. Second, after learning, the retention and/or proper retrieval of newly acquired memory critically depend on the β‐adrenergic modulation of long‐term memory consolidation. Third, the reconsolidation of previously established FM discrimination memory after retrieval in a retraining session, though relying on mechanisms that may differ from those recruited during the consolidation of newly acquired memory, also requires β‐adrenergic activity in the auditory cortex during a narrow post‐session time window. A more comprehensive model of modulatory processes of memory management by the auditory cortex is presented in Figure S12. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Similar articles

See all similar articles

Cited by 1 article

References

    1. Ahmadiantehrani S., & London S. E. (2017). Bidirectional manipulation of mTOR signaling disrupts socially mediated vocal learning in juvenile songbirds. Proceedings of the National Academy of Sciences, 114, 9463–9468. - PMC - PubMed
    1. Aitkin L. (1990). The auditory cortex. London, UK: Chapman and Hall.
    1. Alberini C. M., & Ledoux J. E. (2013). Memory reconsolidation. Current Biology, 23, R746–R750. - PubMed
    1. Andrzejewski M. E., McKee B. L., Baldwin A. E., Burns L., & Hernandez P. (2013). The clinical relevance of neuroplasticity in corticostriatal networks during operant learning. Neuroscience and Biobehavioral Reviews, 37, 2071–2080. - PMC - PubMed
    1. Angeloni C., & Geffen M. N. (2018). Contextual modulation of sound processing in the auditory cortex. Current Opinion in Neurobiology, 49, 8–15. - PMC - PubMed
Feedback