Acquisition, extinction, and reacquisition of a cerebellar cortical memory trace.
Associative learning in the cerebellum underlies motor memories and probably also cognitive associations. Pavlovian eyeblink conditioning, a widely used experimental model of such learning, depends on the cerebellum, but the memory locus within the cerebellum as well as the underlying mechanisms have remained controversial. To date, crucial information on how cerebellar Purkinje cells change their activity during learning has been ambiguous and contradictory, and there is no information at all about how they behave during extinction and reacquisition. We have now tracked the activity of single Purkinje cells with microelectrodes for up to 16 h in decerebrate ferrets during learning, extinction, and relearning. We demonstrate that paired peripheral forelimb and periocular stimulation, as well as paired direct stimulation of cerebellar afferent pathways (mossy and climbing fibers) consistently causes a gradual acquisition of an inhibitory response in Purkinje cell simple spike firing. This conditioned cell response has several properties that matches known features of the behavioral conditioned response. The response latency varies with the interstimulus interval, and the response maximum is adaptively timed to precede the unconditioned stimulus. Across training trials, it matches behavioral extinction to unpaired stimulation and also the substantial savings that occur when paired stimulation is reinstated. These data suggest that many of the basic behavioral phenomena in eyeblink conditioning can be explained at the level of the single Purkinje cell.
Jirenhed
Dan-Anders
DA
Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden. dan-anders.jirenhed@med.lu.se
Bengtsson
Fredrik
F
Hesslow
Germund
G
D000200:Action Potentials; D000818:Animals; D001767:Blinking / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D004558:Electric Stimulation; D005108:Extinction, Psychological / Q000502:physiology*; D005289:Ferrets; D005552:Forelimb / Q000502:physiology; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009412:Nerve Fibers / Q000502:physiology; D009847:Olivary Nucleus / Q000502:physiology; D009915:Orbit / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology; D013997:Time Factors