How does 5-HT1AR deficiency lead to altered hippocampal oscillations?
From the limited literature on serotonergic effects on ripple oscillations, it seems likely that a decrease in ripple amplitude cannot be explained by a simple lack of the receptor in the adult. It is difficult to reconcile decreased ripple size, which suggests less excitation of CA1 pyramidal neurons (Csicsvari et al., 1999), with the absence of an inhibitory receptor. A recent report showed that pharmacological blockade of the 5-HT1AR with the specific antagonist WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl)cyclo-hexane carboxamide trihydrochloride) resulted in less frequent but normal-sized ripples (Ponomarenko et al., 2003) as opposed to the smaller but equally frequent ripples seen here in the knock-outs. These data argue that the change in ripple size seen in the knock-outs is likely attributable to an indirect effect of 5-HT1AR deletion, perhaps as a consequence of altered hippocampal development. Alternatively, serotonergic drugs are known to affec
