Auditory associative memory and representational plasticity in the primary auditory cortex

Abstract

Historically, the primary auditory cortex has been largely ignored as a substrate of auditory memory, perhaps because studies of associative learning could not reveal the plasticity of receptive fields (RFs). The use of a unified experimental design, in which RFs are obtained before and after standard training (e.g., classical and instrumental conditioning) revealed associative representational plasticity, characterized by facilitation of responses to tonal conditioned stimuli (CSs) at the expense of other frequencies, producing CS-specific tuning shifts. Associative representational plasticity (ARP) possesses the major attributes of associative memory: it is highly specific, discriminative, rapidly acquired, consolidates over hours and days and can be retained indefinitely. The nucleus basalis cholinergic system is sufficient both for the induction of ARP and for the induction of specific auditory memory, including control of the amount of remembered acoustic details. Extant controversies regarding the form, function and neural substrates of ARP appear largely to reflect different assumptions, which are explicitly discussed. The view that the forms of plasticity are task dependent is supported by ongoing studies in which auditory learning involves CS-specific decreases in threshold or bandwidth without affecting frequency tuning. Future research needs to focus on the factors that determine ARP and their functions in hearing and in auditory memory.

Figure 1

Classical conditioning produces CS-specific facilitation and tuning shifts. (A) An example of a complete shift of frequency tuning of a single cell in A1 of the guinea pig, from a pre-training best frequency (BF) of 0.75 kHz to the CS frequency of 2.5 kHz after 30 trials of conditioning. Inset shows pre- and post-training post-stimulus time histograms (PSTHs) for the pre-training BF and the CS frequencies. (B) Double-peaked tuning, with pre-training BFs at 5.0 and 8.0 kHz. The CS was selected to be 6.0 kHz, a low point. After conditioning (30 trials), responses to the CS frequency increased to become the peak of tuning. (C) A cell that exhibited minimal or no response to tones before tuning developed tuning specifically to the CS frequency after conditioning (30 trials).

Figure 2

Additional attributes of associative representational plasticity. (A) Two-tone discrimination. Representation of neuronal responses in A1 before, immediately after and one hour after two-tone discrimination training (30 each CS+ [22.0 kHz] and CS− [39 kHz] intermixed trials). Displayed are rates of discharge (Y-axis) as a function of tonal frequency (X-axis) and level of testing stimuli (10–70 dB). Note that conditioning changed the “topography” of neuronal response. The pre-training best frequency of 27.0 kHz suffered a reduction in response as did the CS− frequency. In contrast, responses to the CS+ frequency increased. Note consolidation, in the form of a continued development of these changes; after one hour of silence, the only excitatory response is at the CS+ frequency. (B) Rapid development of RF plasticity. Vector diagram of increase in response to the CS frequency and decrease in response to the pre-training BF after 5, 15, 30 training trials and one hour later. Note specific facilitation to CS frequency after only 5 trials and the consolidation after 1 hour of silence. (C) Long term retention and stability of RF plasticity over weeks.

Figure 3

Summary of the effects of conditioning, sensitization and habituation on frequency receptive fields in the primary auditory cortex of the guinea pig. Data are normalized to octave distance from (A) the CS frequency, (B) the pre-sensitization best frequency or (C) the repeated frequency. Note that conditioning produces a CS-specific increased response whereas sensitization (tone–shock or light–shock unpaired) produces general increases across the spectrum. Habituation produces frequency-specific decreased response.

Figure 4

CS-specific auditory memory and control of memory detail, induced by tone paired with stimulation of the nucleus basalis (respiration responses to post-training tone and generalization gradients). (A) Individual respiration records (with value of respiration change index, RCI) to three frequencies (2, 6 and 12 kHz) for one animal each from the paired and unpaired groups. The largest response was at the CS frequency of 6 kHz for the paired animal (RCI = 0.50). Horizontal bar indicates tone duration. (B) Left panel, group mean (± SE) change in respiration to all tones for both groups. Note that the maximal response was at 6 kHz for the paired group, but not for the unpaired group. The group difference function (paired minus unpaired) (right panel) shows a high degree of specificity of respiratory responses to 6 kHz. (C) Level of NB stimulation controls specificity of contents of memory. Pre-training responses to test tones in the Moderate and Weak NB stimulation (NBs) groups. (D) Post-training responses for the Moderate NBs groups. Note the significant difference between the paired and unpaired groups, confined to the CS-band frequencies. This indicates that training with a moderate level of NBs produced memory that was both associative and CS-specific. (E) Comparisons of changes within the Moderate group (post- minus pre-training responses to test tones). Note that the paired group had developed a significant increase to the CS-band frequencies only, while the unpaired group had developed a significant decrease, probably indicating frequency-specific habituation due to lack of pairing with NB stimulation. (F) Post-training responses for the Weak NBs groups. In contrast to the Moderate NBs group, pairing produced a significant difference in response across all test frequencies compared to its unpaired controls. This indicates that training with weak NBs was sufficient to produce associative memory but insufficient to produce memory for frequency detail, i.e., memory that the frequency of the CS was paired with NBs. (G) Comparisons of changes within the Weak NBs groups showed that the paired group did not develop absolute increased responses but that the unpaired group did develop significant decreases in responses across the spectrum of test frequencies. Thus, pairing the CS with weak NBs apparently prevented a habituatory decrement in the Weak paired group, which is evident in the Weak unpaired group.

Figure 5

The model of ARP and autonomic conditioned responses based on convergence of the CS and US in the magnocellular medial geniculate. This model hypothesizes the minimal circuitry that would be sufficient to account for short and long term associative representational plasticity and rapidly-acquired conditioned autonomic responses. See text for details.

Figure 6

Learning without plasticity of frequency processing. The development of ARP, in the form of CS-specific reduction of threshold and bandwidth, depends on “modest” change in training protocol. (A) Protocol for Easy and Difficult task groups, the latter differing only in the non-punishment/error signal during 2 s at tone offset. (B) The Difficult group never learned to inhibit responses during the 2 s catch period, in contrast to the Easy group which learned to inhibit rapidly; note the difference in Y-axis values. (C) Learning curves showing the retarded acquisition of the Difficult group until the 17^th training day at which time they achieved the same asymptotic performance as the Easy group, by learning to inhibit responses during silence, when error signal was present after 2 s catch period. (Performance = bar presses during the tone divided by total bar presses during intertrial period when error signal was equally present for both groups). Inset: behavioral generalization gradients (without reward) showing same behavior. (D) Frequency response areas (FRAs) with the same CF showing a decrease in threshold and reduction in bandwidth at the CS frequency (5.0 kHz) for Difficult training. (No tuning shifts were found across A1 in this study.) (E) Thresholds and BW20 for Easy, Difficult and Naïve (untrained) groups. The only significant effects were found in the Difficult group: a decrease in threshold (increased sensitivity) and a narrowing of bandwidth (increased selectivity) for octave band containing the CS frequency.