Neural Substrates of Eyeblink Conditioning: Acquisition and Retention

Abstract

Classical conditioning of the eyeblink reflex to a neutral stimulus that predicts an aversive stimulus is a basic form of associative learning. Acquisition and retention of this learned response require the cerebellum and associated sensory and motor pathways and engage several other brain regions including the hippocampus, neocortex, neostriatum, septum, and amygdala. The cerebellum and its associated circuitry form the essential neural system for delay eyeblink conditioning. Trace eyeblink conditioning, a learning paradigm in which the conditioned and unconditioned stimuli are noncontiguous, requires both the cerebellum and the hippocampus and exhibits striking parallels to declarative memory formation in humans. Identification of the neural structures critical to the development and maintenance of the conditioned eyeblink response is an essential precursor to the investigation of the mechanisms responsible for the formation of these associative memories. In this review, we describe the evidence used to identify the neural substrates of classical eyeblink conditioning and potential mechanisms of memory formation in critical regions of the hippocampus and cerebellum. Addressing a central goal of behavioral neuroscience, exploitation of this simple yet robust model of learning and memory has yielded one of the most comprehensive descriptions to date of the physical basis of a learned behavior in mammals.

Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs

“…However, the two-way repeated measures ANOVA confirmed that the CR% ( Figure 5A, right panel) and the CR peak amplitude ( Figure 5B, right panel) for the animals that received the muscimol infusion were significantly lower than for the animals that received the saline infusion [F (1,16) Effects of muscimol infusion into the left cerebellar interpositus nucleus on long TEC expression Infusion of muscimol into the left cerebellar interpositus nucleus significantly decreased the CR% ( Figure 6A, right panel) and the CR peak amplitude ( Figure 6B, right panel) for the group that received long-trace conditioning. A twoway repeated measures ANOVA performed on CR% ( Figure 6A, left panel) and CR peak amplitude ( Figure 6B, left panel) revealed that there was no significant effect of trial block [F (1,14) =0.007, P=0.933 and F (1,14) =0.089, P=0.770, respectively] during the pre-infusion block (trial blocks 1-3). In contrast, the two-way repeated measures ANOVA confirmed that the CR% ( Figure 6A, right panel) and the CR peak amplitude ( Figure 6B, right panel) for the animals that received the muscimol infusion were significantly lower than for the animals that received the saline infusion [F (1,14) =25.801, P<0.001 and …”

“…A twoway repeated measures ANOVA performed on CR% ( Figure 5A, left panel) and CR peak amplitude ( Figure 5B, left panel) revealed that there was no significant effect of trial block [F (1,16) =0.250, P=0.624 and F (1,16) =0.516, P=0.483, respectively] during the pre-infusion block (trial blocks 1-3). However, the two-way repeated measures ANOVA confirmed that the CR% ( Figure 5A, right panel) and the CR peak amplitude ( Figure 5B, right panel) for the animals that received the muscimol infusion were significantly lower than for the animals that received the saline infusion [F (1,16) Effects of muscimol infusion into the left cerebellar interpositus nucleus on long TEC expression Infusion of muscimol into the left cerebellar interpositus nucleus significantly decreased the CR% ( Figure 6A, right panel) and the CR peak amplitude ( Figure 6B, right panel) for the group that received long-trace conditioning. A twoway repeated measures ANOVA performed on CR% ( Figure 6A, left panel) and CR peak amplitude ( Figure 6B, left panel) revealed that there was no significant effect of trial block [F (1,14) =0.007, P=0.933 and F (1,14) =0.089, P=0.770, respectively] during the pre-infusion block (trial blocks 1-3).…”

“…A twoway repeated measures ANOVA performed on CR% (Figure 4A, left panel) and CR peak amplitude ( Figure 4B, left panel) revealed there was no significant effect of trial block [F (1,14) =0.299, P=0.593 and F (1,14) =0.028, P=0.870, respectively] during the pre-infusion block (trial blocks 1-3). However, the two-way repeated measures ANOVA confirmed that the CR% ( Figure 4A, right panel) and the CR peak amplitude ( Figure 4B, right panel) for the animals that received the muscimol infusion were significantly lower than those observed for the animals that received the saline infusion [F (1,14) =25.599, P<0.001 and F (1,14) =36.147, P<0.001, respectively] during the post-infusion block (trial blocks 4-8).…”

“…Classical eyeblink conditioning is one of the most widely used model systems for studying the behavioral and neurobiological mechanisms of associative learning and memory [1][2][3] . All variant of eyeblink conditioning involve paired presentations of a behaviorally neutral conditioned stimulus (CS; eg, a tone or light) and an unconditioned stimulus (US; eg, a corneal airpuff or periorbital shock).…”

Awareness is essential for differential delay eyeblink conditioning with soft-tone but not loud-tone conditioned stimuli

“…Classical conditioning of the eyeblink response serves as an excellent model in which to investigate the mechanisms of associative learning and memory in mammals [2][3][4][5][6][7][8][9] . In this paradigm, a conditioned stimulus (CS; e.g., a tone or light) is followed by an unconditioned stimulus (US; e.g., a corneal air-puff or periorbital shock).…”