The level of cholinergic nucleus basalis activation controls the specificity of auditory associative memory

Abstract

Learning involves not only the establishment of memory per se, but also the specific details of its contents. In classical conditioning, the former concerns whether an association was learned while the latter discloses what was learned. The neural bases of associativity have been studied extensively while neural mechanisms of memory specificity have been neglected. Stimulation of the cholinergic nucleus basalis (NBs) paired with a preceding tone induces CS-specific associative memory. As different levels of acetylcholine may be released naturally during different learning situations, we asked whether the level of activation of the cholinergic neuromodulatory system can control the degree of detail that is encoded and retrieved. Adult male rats were tested pre-and post-training for behavioral responses (interruption of ongoing respiration) to tones of various frequencies (1-15 kHz, 70 dB, 2 s). Training consisted of 200 trials/day of tone (8.0 kHz, 70 dB, 2 s) either paired or unpaired with NBs (CS-NBs = 1.8 s) at moderate (65.7 ± 9.0 μA, one day) or weak (46.7 ± 12.1 μA, three training days) levels of stimulation, under conditions of controlled behavioral state (pre-trial stable respiration rate). Post-training (24 h) responses to tones revealed that moderate activation induced both associative and CS-specific behavioral memory, whereas weak activation produced associative memory lacking frequency specificity. The degree of memory specificity 24 h after training was positively correlated with the magnitude of CS-elicited increase in γ activity within the EEG during training, but only in the moderate NBs group. Thus, a low level of acetylcholine released by the nucleus basalis during learning is sufficient to induce associativity whereas a higher level of release enables the storage of greater experiential detail. γ waves, which are thought to reflect the coordinated activity of cortical cells, appear to index the encoding of CS detail. The findings demonstrate that the amount of detail in memory can be directly controlled by neural intervention.

Specific auditory memory induced by nucleus basalis stimulation depends on intrinsic acetylcholine

“…However, after training, the Saline animal displayed a large response to the CS frequency, but still no responses to the other tones. This pattern of response change is typical of NB-induced behavioral memory (McLin et al, 2002a;Miasnikov et al, 2006;Weinberger et al, 2006). In contrast, the Scopolamine subject displayed neither posttraining response to the CS frequency, nor to the other frequencies.…”

“…The materials and methods were generally the same as those previously reported (Miasnikov et al, , 2008Weinberger et al, 2006), and thus will be described only briefly. All procedures were performed in accordance with the University of California Irvine Animal Research Committee and the NIH Animal Welfare guidelines.…”

Dynamic changes of rodent somatosensory barrel cortex are correlated with learning a novel conditioned stimulus

“…Our results resemble these effects and may reflect a similar neurophysiological origin. Notably, in vivo work pairing nucleus basalis stimulation with the presentation of a tone induces changes in the primary auditory cortex of rats resembling those elicited by conditioning (Weinberger et al 2006). Moreover, work by Froemke et al (2007), recording from the primary auditory cortex of anesthetized rats, demonstrated a possible functional role for an asynchronous perturbation and rebalancing of inhibition and excitation within the primary auditory cortex.…”

Motivationally neutral stimulation of the nucleus basalis induces specific behavioral memory

“…The group data are shown in Figure 2B. Note the marked activation of several seconds duration of the "All Bands" EEG, involving large decreased activity in the alpha band (8.8 -14.6 Hz) and increased activity in the gamma band (33.0 -59.0 Hz) (McLin, Miasnikov, & Weinberger, 2002b;Miasnikov et al, 2006;Rasmusson et al, 1992;Weinberger et al, 2006). It might be argued that EEG activation during tone-NBstm training sessions was caused by the CS tone rather than by NBstm.…”

“…We did not include such a control group because prior studies using paired NBstm have been shown to produce associative memory. That is, non-associative control groups failed to develop specific behavioral memory, whether assessed by changes in respiration or heart rate, or whether employing 2,000 trials over days or 200 trials in a single day (McLin et al, 2002a;Miasnikov et al, 2006;Weinberger et al, 2006). In fact, subjects receiving random tone and NBstm develop decreased responses to the CS frequency , which is characteristic of habituation (Condon & Weinberger, 1991;Thompson & Spencer, 1966).…”