Selective suppression of excitatory synapses on GABAergic interneurons by norepinephrine in juvenile rat prefrontal cortical microcircuitry

Abstract

The noradrenergic system of the brain is thought to facilitate neuronal processes that promote behavioral activation, alertness, and attention. It is known that norepinephrine (NE) can be significantly elevated in the prefrontal cortex under normal conditions such as arousal and attention, and following administration of psychostimulants and various other drugs prescribed for psychiatric disorders. However, how NE modulates neuronal activity and synapses in the local prefrontal circuitry remains elusive. In this study, we characterized the actions of NE on individual monosynaptic connections among layer V pyramidal neurons (P) and fast-spiking (FS) GABAergic interneurons in the juvenile (postnatal days 20–23) rat prefrontal local circuitry. We found that NE selectively depresses excitatory synaptic transmission in P-FS connections but has no detectable effect on the excitatory synapses in P-P connections and the inhibitory synapses in FS-P connections. NE apparently exerts distinctly different modulatory actions on identified synapses that target GABAergic interneurons but has no effect on those in the pyramidal neurons in this specific developmental period. These results indicate that, depending on the postsynaptic targets, the effects of NE in prefrontal cortex are synapse-specific, at least in the juvenile animals.

Noradrenergic α1-Adrenoceptor Actions in the Primate Dorsolateral Prefrontal Cortex

“…Therefore, the ascending side of the inverted-U dose response curve would be accentuated in these preparations and, indeed, these studies find excitatory effects of ␣1-AR stimulation involving both increased presynaptic glutamate release (Zhang et al, 2013;Luo et al, 2014) and facilitation of postsynaptic NMDAR and AMPAR actions (Luo et al, 2014). In vitro studies of rat mPFC have also found that ␣1-AR can reduce glutamatergic drive on GABA interneurons (Wang et al, 2013a), which may disinhibit cortex.…”

The α2A‐adrenoceptor suppresses excitatory synaptic transmission to both excitatory and inhibitory neurons in layer 4 barrel cortex

“…; Wang et al . ) and the hippocampus (Scanziani et al . ) and β 1 ‐adrenoceptors (β 1 ‐ARs) in the prefrontal cortex (Luo et al .…”

“…; Wang et al . ), visual (Kobayashi, ) and auditory cortices (Dinh et al . ) and, further, the cerebellum (Carey & Regehr, ; Lippiello et al .…”

Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex

“…In particular, NE selectively depresses excitatory synaptic transmission in pyramidal (P)–FS connections but has no detectable effect on the excitatory synapses in P–P connections and the inhibitory synapses in FS–P connections. In this case, NE exerts distinctly different modulatory actions on identified synapses that target GABAergic interneurons but has no effect on those in the pyramidal neurons in the developing (juvenile) rat mPFC (Wang et al, 2013). …”

“…To address this issue, we examined the effects of NE on monosynaptically connected and individually identified synaptic connections in layer V of mPFC slices by using quadruple patch clamp recordings conducted with DA application (Gao et al, 2001; Gao and Goldman-Rakic, 2003; Gao et al, 2003). The results indicated that NE selectively depresses excitatory synaptic transmission in pyramidal neuron–FS interneuron (P-NP) connections, but has no apparent effect on the excitatory synapses on the pyramidal neuron–pyramidal neuron connection (P-P) and on the inhibitory synapses in the FS interneuron–pyramidal neuron connections (NP-P) (Wang et al, 2013). Together with the action of DA on these connections (Gao et al, 2001; Gao and Goldman-Rakic, 2003; Gao et al, 2003), we propose a complementary effect of NE and DA on the synaptic communications between pyramidal neurons and FS interneurons in the local prefrontal circuitry as shown in Figure 3.…”