Purkinje Cell Loss by OX7-Saporin Impairs Excitatory and Inhibitory Eyeblink Conditioning.

Abstract

Cerebellar cortical contributions to eyeblink conditioned excitation have been examined extensively. In contrast, very little evidence exists concerning the role of the cerebellar cortex in eyeblink conditioned inhibition. In the current study, rats were given intraventricular infusions of the immunotoxin OX7-saporin to selectively destroy Purkinje cells throughout the cerebellar cortex following excitatory conditioning. After a 2-week postinfusion period, the rats were given reacquisition training. After reacquiring excitatory conditioning, the rats were trained in a featurenegative discrimination procedure to establish conditioned inhibition. Rats treated with OX7-saporin showed impaired reacquisition of excitatory conditioning and acquisition of conditioned inhibition. The results suggest that Purkinje cells play important, but different, roles in conditioned excitation and inhibition in rats.

Differential Effects of Cerebellar Inactivation on Eyeblink Conditioned Excitation and Inhibition

“…One implication of these findings is that eyeblink microzones not affected by muscimol infusions in the current study might be capable of acquiring conditioned inhibition. However, a recent study that depleted Purkinje cells throughout the cerebellar cortex using the immunotoxin OX7-saporin found impaired acquisition of conditioned inhibition, but all rats with Purkinje cell depletion acquired robust CR inhibition (Nolan and Freeman, 2005). The findings of Nolan and Freeman (2005) suggest that cerebellar cortical areas spared in the current study might play a role in conditioned inhibition but extracerebellar structures must also be necessary.…”

Changes in inhibition during differential eyeblink conditioning with increased training

“…The present experiment included control groups for the retardation test that determined the baseline rate for excitatory cross-modal transfer between auditory and visual CSs. These control groups for the retardation test have not previously been included in experiments on inhibitory eyeblink conditioning in rats (e.g., Campolattaro & Freeman, 2006;Freeman et al, 2005;Freeman & Nicholson, 1999;Nicholson & Freeman, 2002;Nolan & Freeman, 2005. A CS X-alone control group was also included in this experiment to determine whether any inhibition acquired by the putative inhibitory stimulus CS (X) during differential inhibition training was due to latent inhibition.…”

“…An open question is whether Pavlovian conditioned inhibition and differential inhibition produce similar amounts of inhibitory learning during eyeblink conditioning with rats. Previous inhibitory learning experiments in rodent eyeblink conditioning have used only Pavlovian conditioned inhibition procedures (Campolattaro & Freeman, 2006;Freeman, Halverson, & Poremba, 2005;Freeman & Nicholson, 1999;Nicholson & Freeman, 2002;Nolan & Freeman, 2005. It may be expected that Pavlovian conditioned inhibition and differential inhibition procedures will produce similar amounts of inhibitory learning in eyeblink conditioning with rats because they have produced equal amounts of inhibitory learning in NM conditioning with rabbits (Mahoney et al, 1975).…”

Perirhinal cortex lesions impair simultaneous but not serial feature-positive discrimination learning.

“…One circuit permitted the delivery of a shock stimulus (1−2 mA, DC constant current) through a stimulus isolator (Model number 365A, World Precision Instruments, Sarasota, FL). EMG activity was recorded differentially, filtered (500−5,000 Hz) and integrated by equipment (JSA Designs, Raleigh, NC) described in other reports (Nicholson & Freeman, 2002b;Nicholson, Sweet, & Freeman, 2003;Nolan & Freeman, 2005).…”