Possible role of intramembrane receptor-receptor interactions in memory and learning via formation of long-lived heterom
Learning in neuronal networks occurs by instructions to the neurons to change their synaptic weights (i.e., efficacies). According to the present model a molecular mechanism that can contribute to change synaptic weights may be represented by multiple int
- PDF / 4,749,509 Bytes
- 28 Pages / 595 x 842 pts (A4) Page_size
- 9 Downloads / 116 Views
o. Franzen2, S. Ferre3, G. Leo, R. Franco4, and K. Fuxe2
1 Department of BioMedical Sciences, Modena, Italy 2Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden 3 Behavioural Neuroscience Branch, NIDA, IRP, NIH, Department of Health and Human Services, Baltimore, MD, USA 4 Department of Biochemistry, University of Barcelona Marti i Franques, Spain 5 Department of Rehabilitation, Ludes Paradiso, Switzerland
Summary. Learning in neuronal networks occurs by instructions to the neurons to change their synaptic weights (i.e., efficacies). According to the present model a molecular mechanism that can contribute to change synaptic weights may be represented by multiple interactions between membrane receptors forming aggregates (receptor mosaics) via oligomerization at both pre- and post-synaptic leveL These assemblies of receptors together with inter alia single receptors, adapter proteins, G-proteins and ion channels form the membrane bound part of a complex three-dimensional (3D) molecular circuit, the cytoplasmic part of which consists especially of protein kinases, protein phosphatases and phosphoproteins. It is suggested that this molecular circuit has the capability to learn and store information. Thus, engram formation will depend on the resetting of 3D molecular circuits via the formation of new receptor mosaics capable of addressing the transduction of the chemical messages impinging on the cell membrane to certain sets of G-proteins. Short-term memory occurs by a transient stabilization of the receptor mosaics producing the appropriate change in the synaptic weight. Engram consolidation (long-term memory) may involve intracellular signals that translocate to the nucleus to cause the activation of immediate early genes and subsequent formation of postulated adapter proteins which stabilize the receptor mosaics with the formation of long-lived heteromeric receptor complexes. The receptor mosaic hypothesis of the engram formation has been formulated in agreement with the Hebbian rule and gives a novel molecular basis for it by postulating that the pre-synaptic activity change in transmitter and modulator release reorganizes the receptor mosaics at post-synaptic level and
* This paper is dedicated to Fiorenzo Stirpe, Professor of General Pathology, and to Eugenio Riva, Professor of Human Physiology, at the University of Bologna, Italy
R. Horowski et al. (eds.), Advances in Research on Neurodegeneration © Springer-Verlag/Wien 2003
2
L. F. Agnati et al.
subsequently at pre-synaptic level with the formation of novel 3D molecular circuits leading to a different integration of chemical signals impinging on preand post-synaptic membranes hence leading to a new value of the synaptic weight. Engram retrieval is brought about by the scanning of the target networks by the highly divergent arousal systems. Hence, a continuous reverberating process occurs both at the level of the neural networks as well as at the level of the 3D molecular circuits within each neuron of the network until the appropriate
Data Loading...
