Monoamines and the modulatory control of spinal sensory processing
|Garraway, Sandra Mary
|Doctor of Philosophy (Ph.D.)
|The descending monoamines serotonin (5-HT), noradrenaline (NA) and dopamine (DA), and acetylcholine (ACh), a spinal monoamine, have been previously shown to exert modulatory control over spinal functions, including nociception. Partly due to the multiple receptor subtypes these transmitters bind to, the mechanisms underlying their actions are not clearly understood. In three interrelated studies, whole-cell patch clamp recordings in a spinal cord slice preparation were conducted to investigate the manner in which the monoamines modify both synaptic responses and cellular properties of deep dorsal horn (DDH) neurons of the neonatal rat. First, the actions of all four transmitters on individual DDH neurons were compared. The results demonstrated that 5-HT, NA and DA similarly depressed synaptic responses, while ACh produced facilitation in most neurons. Though none of these transmitters altered the passive membrane properties of the neurons, they converted neurons with phasic firing properties, in response todepolarizing current steps, to repetitive. Secondly, the actions of several selective S-HT receptor ligands on synaptic responses evoked in two age groups of animals (P3-6, P10-14) were compared. In both age groups, the 5-HT1A receptor agonist produced synaptic depression in most neurons, while the 5-HT3 and 7 receptor agonists produced synaptic facilitation. Additionally, selective antagonism of the 5-HT1A receptor generally facilitated evoked responses, suggesting that sensory transmission to the DDH is tonically inhibited by endogenous 5-HT. Thirdly, since long-term potentiation (LTP) of primary afferent synapses in spinal neurons may represent 'memory modules' that produce long-lasting increases in sensory gain, we studied 5-HT's control over the induction and expression of sensory-evoked synaptic plasticity. 5-HT was tested on evoked synaptic responses before, duri g or after a conditioning stimulation (CS) that produced either UP or long-term depression (LTD). Overall, 5-HT depressed the evoked responses, before or after CS-induced UP and LTD. Importantly, CS in the presence of 5-HT significantly increased the incidence of LTD. These studies suggest that the three descending monoaminergic transmitter systems are organized to exert similar modulatory control over spinal sensory functions. Furthermore, although various mechanisms might be involved, their general action at the cellular level of the spinal cord dorsal horn is depression.
|Monoamines and the modulatory control of spinal sensory processing