Effect of monoclonal antibodies to A3G7 protein specific for cerebellar Purkinje cells and hippocampal pyramidal neurons on learning, consolidation, and retrieval of shortand long-term habituation to acoustic startle reaction is studied in adult rats. Application of 1 mg/ml antibodies to the cerebellar vermis selectively disturbs long-term habituation, while 2 mg/ml antibodies inhibit both short-and long-term habituation. The data are analyzed with consideration of the involvement of A3G7 protein into nerve growth and neurotransmittory processes underlying learning and memory in developing and mature brain.
Key Words: monoclonal antibodies; nerve growth factor; learning; memory; acoustic startle reactionThis study stemmed from the concept on the involvement of molecular factors that regulate growth and development of the nervous tissue into learning and memory in mature brain [4,9,12]. Of special interest are the factors regulating the differentiation of some neurons and associated with synapto-and dendritogenesis. These processes underlie integrative functions of the nervous system both in young and adult organism [6,131. We have previously obtained monoclonal antibodies (MAB) to neurospecific A3G7 protein localized in rat cerebellar Purkinje cells and hippocampal pyramidal neurons and involved into formation and stabilization of synaptic contacts [3]. It has been shown that anti-A3G7 MAB block induction of the long-term potentiation in hippocampal slices of adult rats and impair the active avoidance reaction in adult rats one day postinjection [1,5]. However, the role of A3G7 protein in learning and Laboratory of Functional Neurochemistry, P. K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Moscow; Instilute of Medical and Biological Cybernetics, Siberian Division of 1tlo Russian Academy of Medical Sciences, Novosibirsk memory remained beyond the scope of these pilot studies. Taking into account the fact that A3G7 is located in cerebellar Purkinje cells, the effect of anti-A3G7 MAB was studied on the mode of habituation to acoustic startle reaction (ASR). Previotts studies demonstrated that medial cerebellar structures (vermis and nucleus fastigii) directly participate in ASR habituation in adult rats [7,11].The aim of the present study was to investigate the effect of anti-A3G7 MAB on acquisition, consolidation, and retrieval of short-and long-term ASR habituation in adult rats under condition of MAB application to the vermis.
MATERIALS AND METHODSExperiments were carried out on male Wistar rats weighing 250-300 g and maintained with food and water ad libitum (3 rats per cage). Experiments were performed in the light period from 11:00 to 15:00 Short-and long-term habituation to ASR was used as the behavioral model. Twenty-for hours before the experiment, the animals were adapted to experimental chamber for 5 min in the absence of stimuli.0007-4888/98/0008-08135"2_0,00 ~'~1999 Kluwer Acddeniic/Ph'nilnl lhllJli~h~'r~