Serotonin Modulates Fast-Spiking Interneuron and Synchronous Activity in the Rat Prefrontal Cortex through 5-HT_1Aand 5-HT_2AReceptors

Fluoxetine (Prozac) and Serotonin Act on Excitatory Synaptic Transmission to Suppress Single Layer 2/3 Pyramidal Neuron-Triggered Cell Assemblies in the Human Prefrontal Cortex

“…A plausible explanation for the suppression of feedforward excitation by fluoxetine and 5-HT is the serotonergic hyperpolarization of GABAergic neurons. The firing of fast spiking GABAergic in-terneurons in the rat can be increased in response to 5-HT and fluoxetine via 5-HT 2 receptors (Zhong and Yan, 2011) making this scenario unlikely, but fast spiking cells containing 5HT-1A receptors could also be downregulated as demonstrated in vivo (Puig et al, 2010). In our sample, GABAergic neurons showed various electrophysiological and morphological properties.…”

“…However, in contrast to what was found in rodents (Foehring et al, 2002;Xiang and Prince, 2003), membrane potentials of various interneuron types were uniformly depolarized in response to 5-HT which could be attributed to restricted sampling or to interspecies differences. Indeed, interspecies differences might exist, since 5HT-1A receptor mRNA was shown to be expressed in a much larger fraction of parvalbumin-expressing neurons, mainly corresponding to basket and axoaxonic cells, in the rat compared with the primate prefrontal cortex (de Almeida and Mengod, 2008;Puig et al, 2010). Our results are in agreement with previous studies achieved by extracellular stimulation in the rat entorhinal cortex (Schmitz et al, 1998a) showing that the 5-HT sensitivity of polysynaptic events was due to the suppression of glutamatergic inputs arriving to interneurons, while GABAergic outputs were not modulated.…”

“…The prefrontal cortex is enriched in 5HT-1A, 5HT-2A and 5-HT 3 receptors in rodents, primates and humans (Jakab and Goldman-Rakic, 2000;DeFelipe et al, 2001;Celada et al, 2004;Santana et al, 2004;de Almeida and Mengod, 2007;Puig et al, 2010). We examined how selective activation of 5-HT receptors influences poly-and monosynaptic events triggered by pyramidal or AACs.…”

Serotonergic Modulation of the Prefrontal Cortex: From Neurons to Brain Waves

“…For instance, 60% of pyramidal neurons in the rat prefrontal cortex express serotonin receptors 5-HT1A or 5-HT2A, particularly in layer 5 (De Almeida & Mengod, 2007;Kia et al, 1996;Lopez-Gimenez et al, 1997;Martin-Ruiz et al, 2001;Pazos & Palacios, 1985;Pompeiano et al, 1992Pompeiano et al, , 1994Santana et al, 2004;Weber & Andrade, 2010;Willins et al, 1997). Interestingly, around 80% of these co-express both receptors (Amargos-Bosch et al, 2004;Puig et al, 2010;Santana et al, 2004), although 5-HT1A receptors reduce whereas 5-HT2A receptors increase neuronal spiking (see below). The purpose of this co-expression has yet to be elucidated.…”

“…5-HT1A receptors are densely located on the axon initial segment (De Felipe et al, 2001), where they may downregulate the generation of action potentials; by contrast, 5-HT2A receptors are abundant on the apical dendrites (Jakab & Goldman-Rakic, 1998;Martin-Ruiz et al, 2001), where they increase excitatory currents (Marek & Aghajanian, 1999) (Figure 1). We have recently found that pyramidal neurons also express 5-HT2C receptors, but the degree of co-expression with 5-HT1A and 5-HT2A receptors is still unknown (Puig et al, 2010). Cortical GABAergic interneurons are also innervated by serotonergic afferents from the raphe nuclei, as assessed by electron microscopy (De Felipe et al, 1991;Smiley & GoldmanRakic, 1996).…”