The physiological and cognitive states of the brain are influenced by variations in the activity of the cholinergic systems. For example, changes in the levels of ACh have been associated with arousal/sleep cycle, sustained and focal attention. Moreover interfering with cholinergic transmission affects learning and cellular plasticity. Despite cholinergic system exerts its action by modifying the extracellular cortical concentration of acetylcholine (ACh) few investigations have until now tested if and how variation in ACh concentrations could influence neuronal synaptic efficacy and plasticity in acute brain preparation. In order to investigate this aspect we have used a quantitative experimental approach (variations in the levels of cholinergic activity) rather than a simply qualitative (absence or presence of cholinergic activity) on rodent visual cortex slices. We found that the extracellular ACh concentration affected in opposite way cortical synaptic efficacy, producing either an enhancement or an inhibition of evoked field potentials (FPs) respectively with low or high concentrations of exogenously applied ACh. The versus of ACh modulatory action was dependent on the activity of AChE and relayed on specific subtypes of muscarinic acetylcholine receptors (mAChRs), thus linking the action of ACh to the activation of particular receptor subtypes. The demonstration of a synaptic-pathway specificity of ACh modulatory action, suggests that cholinergic release could control, in a dynamic way, the flow of cortical information. Moreover, we showed that ACh concentration in cortical tissue contributes to modulate long term changes of synaptic efficacy, such as LTP or LTD induced by specific patterns of afferent neuronal activity. We found that: 1) in the absence of muscarinic receptors activation LTP is not inducible as shown in slices treated with atropine, 2)cholinergic action on cortical L TP depends on the activation of the even (M2, M,i) mAChRs. In addition, the sign of long term change, whether L TP or LTD, appears to be depend on the endogenous level of ACh; indeed, we reported that burst stimulation of afferent neurons, in rats with reduced cortical cholinergic innervation, induces an LTD instead of LTP. These results suggest that the degree of activation of cholinergic system could control cortical the direction of synaptic plasticity in visual cortex.
|Titolo:||Cholinergic modulation of synaptic transmission and plasticity|
|Relatore/i esterni:||Domenici, Luciano|
|Data di pubblicazione:||17-dic-2004|
|Appare nelle tipologie:||8.1 PhD thesis|