Locus coeruleus stimulation and noradrenergic modulation of hippocampo-prefrontal cortex long-term potentiation

Abstract

Stimulation of the subiculum/CA1 of the hippocampal formation evokes monosynaptic field potentials in the prefrontal cortex (PFC). High-frequency stimulation of the hippocampus (HPC) can induce long-term potentiation (LTP) in this hippocampo-prefrontal cortical (hippo-PFC) pathway. Previous studies have shown that dopamine and serotonin modulate hippo-PFC LTP. Here, we investigated whether the locus coeruleus (LC) and noradrenaline (NA) can modulate LTP in the rat hippo-PFC pathway. Stimulation of the LC in combination with stimulation of the HPC increased hippo-PFC LTP. Infusion of lidocaine into the LC reduced hippo-PFC LTP. Administration of the noradrenaline reuptake inhibitor, nisoxetine or the alpha2 adrenoceptor antagonist, idazoxan prior to high-frequency stimulation of the HPC enhanced hippo-LTP. In contrast, administration of clonidine, an alpha2 adrenoceptor agonist, impaired hippo-PFC LTP. Partial noradrenergic (NAergic) lesioning with DSP-4 also impaired hippo-PFC LTP. In conclusion, the LC and NAergic mechanisms modulate hippo-PFC LTP.

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

“…This effect was enhanced by administration of an α 2 receptor antagonist, idazoxan, prior to high-frequency stimulation of the hippocampus, but impaired by administration of the α 2 receptor agonist, clonidine. These data indicate that NE modulates hippo-PFC LTP and thus potentially affects PFC function (Lim et al, 2010). NE has also repeatedly been reported to enhance long-lasting modifications in synaptic efficacy in both the dentate gyrus and CA1 region of the hippocampus (Hopkins and Johnston, 1984; Stanton and Sarvey, 1985), likely via activation of β receptors (Hopkins and Johnston, 1988; Lin et al, 2003; Qian et al, 2012).…”

Stress In Utero: Prenatal Programming of Brain Plasticity and Cognition

“…However, the contribution of other stress mediators such as monoamines should not be underestimated. Stress releases norepinephrine (NE) from fibers originating in the locus coeruleus (70), and long-term changes in monoaminergic neurotransmission have been reported following stress (71). Findings in primates indicate that chronic unpredictable stress during pregnancy has long-lasting effects on noradrenergic and dopaminergic activity and behavior in the offspring.…”

The hippocampo-prefrontal pathway: a possible therapeutic target for negative and cognitive symptoms of schizophrenia

“…Conversely pharmacological inactivation of LC with lidocaine or noradrenergic depletion in PFC also significantly reduced the magnitude of LTP but did not completely block the induction of LTP in anesthetized or freely moving rats. On the same line, systemic administration of nisoxetine (a noradrenaline reuptake inhibitor) and clonidine (α2 adrenergic receptor agonist) augmented and partially blocked LTP in the H-PFC pathway in vivo [41]. There is contrasting evidence on the role of serotonin on H-PFC pathway.…”