Associative representational plasticity in the auditory cortex: a synthesis of two disciplines

Abstract

Historically, sensory systems have been largely ignored as potential loci of information storage in the neurobiology of learning and memory. They continued to be relegated to the role of "sensory analyzers" despite consistent findings of associatively induced enhancement of responses in primary sensory cortices to behaviorally important signal stimuli, such as conditioned stimuli (CS), during classical conditioning. This disregard may have been promoted by the fact that the brain was interrogated using only one or two stimuli, e.g., a CS(+) sometimes with a CS(-), providing little insight into the specificity of neural plasticity. This review describes a novel approach that synthesizes the basic experimental designs of the experimental psychology of learning with that of sensory neurophysiology. By probing the brain with a large stimulus set before and after learning, this unified method has revealed that associative processes produce highly specific changes in the receptive fields of cells in the primary auditory cortex (A1). This associative representational plasticity (ARP) selectively facilitates responses to tonal CSs at the expense of other frequencies, producing tuning shifts toward and to the CS and expanded representation of CS frequencies in the tonotopic map of A1. ARPs have the major characteristics of associative memory: They are highly specific, discriminative, rapidly acquired, exhibit consolidation over hours and days, and can be retained indefinitely. Evidence to date suggests that ARPs encode the level of acquired behavioral importance of stimuli. The nucleus basalis cholinergic system is sufficient both for the induction of ARPs and the induction of specific auditory memory. Investigation of ARPs has attracted workers with diverse backgrounds, often resulting in behavioral approaches that yield data that are difficult to interpret. The advantages of studying associative representational plasticity are emphasized, as is the need for greater behavioral sophistication.

Figure 1

The fundamental paradigms of the disciplines of sensory neurophysiology and the experimental psychology of learning/memory may be viewed as complementary. This entails recognition that stimulus parameters have two basic properties: physical and psychological. Each discipline usually manipulates one of these while holding the other constant.

Figure 2

Receptive field analysis reveals whether learning-induced plasticity is general to the dimension of a conditioned stimulus or specific to the value of the CS. (A). During training trials, one can determine whether or not responses to the CS changed; in this case, they increased. However, both general and specific plasticity could produce this result. (B). A general change revealed by receptive field analysis before and after conditioning. (C). A CS-specific instance of associative representational plasticity, in which responses to many non-CS frequencies are reduced, producing a shift in tuning to the frequency of the CS.

Figure 3

Behavioral verification of associative learning in classical conditioning. Cardiac activity (changes in heart rate to a tone) are shown for two groups of guinea pigs. First, both groups received a tone unpaired with shock for 10 trials (Sens), which resulted in an initial decrease in heart rate during the first block of five trials; this response was no longer present during the second block, perhaps indicating habituation to the tone. Subsequently, one group (Condit) received tone paired with shock, while the other (Sens) continued to receive tone and shock unpaired. Conditioning produced cardiac deceleration CRs as soon as the first block of pairing, which continued to develop across trials. In contrast, the sensitization group showed no such growth of the CR. Such behavioral findings were used to validate the development of a CS−US association, not for purposes of determining CS−CR circuitry (see text).

Figure 4

Classical conditioning produces tuning shifts. 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 tone–shock pairing, during which the guinea pig developed a cardiac conditioned response. Inset shows pre- and post-training poststimulus time histograms (PSTHs) for the pre-training BF and the CS frequencies.

Figure 5

Associative processes favor responses to the frequency of the CS in a variety of circumstances. Single-unit recordings from A1 of the guinea pig. (A) 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. (B). A cell that exhibited minimal or no response to tones before tuning developed tuning specifically to the CS frequency after conditioning (30 trials).

Figure 6

Representation of neuronal responses in A1 (A) before, (B) immediately after, and (C) 1 h after two-tone discrimination training. The guinea pig received 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 (y-axis, 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. Strikingly, consolidation, in the form of a continued development of these changes is evident. After a period of 1 h of silence, the only excitatory response is at the CS⁺ frequency.

Figure 7

Summary of the effects of (A) conditioning, (B) sensitization, and (C) habituation on frequency receptive fields in the primary auditory cortex of the guinea pig. Data are normalized to octave distance from the CS frequency (A), the presensitization best frequency (B) or the repeated frequency (C). 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 8

Effect of learning tone-contingent bar-press for water on tonotopic map in A1. Trained rats received water reward for bar-presses in the presence of a 6.0 kHz tone. Illustrations show tonotopic maps and quantifications of percent of total area (octave frequency bands) for a naïve rat (left) and a rat that attained over 90% correct performance (right). Note that training greatly increased the area of representation for the frequency band containing the 6.0 kHz tone signal.

Figure 9

Evidence of a “memory code” for the acquired behavioral importance of sound. Level of tone importance was controlled by the amount of water deprivation; asymptotic performance was significantly correlated with level of deprivation (for details, see Rutkowski and Weinberger 2005). The area of representation of the frequency band containing the 6.0 kHz tone signal increases as a direct function of the level of behavioral importance of the tone, as operationally indexed by the level of correct performance.

Figure 10

Respiration responses to post-training tone and generalization gradients, showing the induction of CS-specific memory after tone paired with stimulation of the nucleus basalis. (A) Examples of 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. (Bleft) Group mean (± SEM) change in respiration to all tones for both groups. The maximal response (left) was at 6 kHz for the paired group, but not for the unpaired group. The generalization gradient for only the paired group was significantly quadratic (P < 0.01), with responses to 6 kHz being of greatest magnitude. The group difference function (right) shows a high degree of specificity of respiratory responses to 6 kHz.

Figure 11

Level of NB stimulation controls specificity of induced memory. Pre-training and post-training responses to test tones in the Moderate and Weak NB stimulation (NBs) groups. (A) Pre-training responses for subjects later trained with either paired or unpaired CS tone and NB stimulation. There were no differences between the groups. (B) 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. (C) 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. (D) 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 with 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. (E) 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. *P< 0.05; **P< 0.01; ***P< 0.005.

Figure 12

The model of Weinberger and colleagues. 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.