Trends in Neurosciences
Volume 31, Issue 2, February 2008, Pages 105-112
Journal home page for Trends in Neurosciences

Review
Where is the trace in trace conditioning?

https://doi.org/10.1016/j.tins.2007.11.006Get rights and content

Intensive mapping of the essential cerebellar brain circuits for Pavlovian eyeblink conditioning appeared relatively complete by 2000, but new data indicate the need for additional differentiation of cerebellar regions and mechanisms coding delay and trace conditioning. This is especially important, as trace conditioning is an experimentally tractable model of declarative learning. The temporal gap in trace eyeblink conditioning may be bridged by forebrain regions through pontine–cerebellar nuclear connections that can bypass cerebellar cortex, whereas a cerebellar cortical long-term-depression-like process appears to be required to support normal delay conditioning. Experiments focusing on the role of cerebellar cortex and deep nuclei in delay versus trace conditioning add perspective on brain substrates of these seemingly similar paradigms, which differ only by a brief stimulus-free time gap between conditioned and unconditioned stimuli. This temporal gap appears to impose forebrain dependencies and differentially engage different cerebellar circuitry during acquisition of conditioned responses.

Section snippets

Delay and trace conditioning paradigms

Neural substrates of Pavlovian eyeblink and fear conditioning are among the most elaborated and best understood of all learning and memory circuits. Continued exploration of these seemingly simple behaviors and their underlying circuitry reveals the exquisite complexity of brain processing even for the most fundamental forms of learning. Tones, lights or somatosensory stimuli usually serve as the conditioned stimulus (CS) that is paired with an unconditioned stimulus (US) such as an air puff to

Traditional perspective of cerebellar cortex in eyeblink classical conditioning

The cerebellar cortex and hippocampus are normally activated in delay eyeblink conditioning [22], but for decades it has been known that hippocampal lesions do not prevent acquisition or retention in the delay paradigm 23, 24, 25. Hippocampal lesions block acquisition and retention of recently acquired learning in trace eyeblink conditioning 26, 27, 28. For some years, the only study examining the effect of cerebellar cortical lesions upon the retention of previously learned trace CRs reported

Trace eyeblink classical conditioning: independent of cerebellar cortex?

The cerebellar interpositus nucleus is essential in trace eyeblink classical conditioning as demonstrated in rabbits with electrolytic lesions [10] and reversible chemical lesions [48]. In rats tested in trace eyeblink conditioning, there was activation in the posterior interpositus nucleus as assessed by a marker of metabolic activity, [14C]2-deoxyglucose [19]. In addition to the interpositus nucleus in trace eyeblink classical conditioning, an intact hippocampus 26, 27, 28, medial prefrontal

Summary and new research directions

The role of the cerebellum in trace eyeblink conditioning has received far less research attention than it has in delay eyeblink conditioning. It appears that forebrain regions are able to bridge the temporal gap in trace conditioning through pontine–cerebellar nuclear connections, but that a cerebellar cortical LTD-like process is required to support normal delay conditioning. Additional studies of cerebellar cortical and nuclear involvement in forebrain-dependent trace eyeblink classical

Acknowledgements

We would like to thank Steven Purcell and Roberto Galvez for their contributions to Figure 1, and Craig Weiss for his contribution to Figure 3. Comments on and suggestions for the manuscript by Indira Raman and Craig Weiss are very much appreciated. This research was supported by grants from the National Institute on Aging, 1 R01 AG021925 and 1 R01 AG023742, to D.S.W-P. and from the National Institute of Mental Health, 1 R01 MH47340, and the National Institute on Aging, 2 R37 AG08796, to J.F.D.

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