Monoaminergic (noradrenergic, dopaminergic and serotonergic) modulation of hippocampal activity is assumed to play a major role in neuronal plasticity, learning and memory. Understanding the locus of action of these neuromodulators at the cellular level will expand our knowledge of their nature and allow us to identify issues related to their dysfunction. In the present work I study the effects of norepinephrine (NE) and dopamine (DA) on spontaneous and evoked activity in patch-clamped neurons of hippocampal slices. Both DA and NE induced a significant decrease in the amplitude of the evoked PSCs recorded from CA1 pyramidal neurons in response to stimulation of the Schaffer collaterals, accompanied by a small decrease in the cell input resistance, and a small hyperpolarization. While decreasing the evoked PSCs, NE promoted an overall increase in spontaneous synaptic activity. Pharmacological assessment of these results indicated an α1 adrenergic receptor involvement in both the decrease of the amplitude of evoked PSCs as well as the increase in spontaneous activity. Surprisingly, the effect of NE on evoked PSCs was partially antagonized by D1 dopaminergic receptor antagonist SCH23390, which suggests that NE activates dopamine receptors. The effect of DA on evoked PSCs was blocked by α1 adrenergic receptor antagonist prazosin, which suggests that DA, in turn, is activating adrenergic receptors.
Noradrenergic system is highly affected by stress; in particular, the differences between NE effects in dorsal and ventral hippocampus (DH and VH, respectively) have been shown to change in stressed animals.
In this work I used two types of stress protocols – Prenatal Stress (PS) and Acute Stress (AS) – to study the effect of stress on monoamine responses in slices of DH and VH. In non-stressed rats, NE effect on the evoked PSCs is larger in DH than in VH. PS and AS rats increased NE effect in VH, thus abolishing the difference between DH and VH. Pharmacological data suggests that these differences result from differential efficiencies of α1 and D1 receptors between DH and VH of both control and PS rats. Acute stress reversed the difference between PS and control rats; in the AS slices the PSC reduction was significantly different between DH and VH of PS rats, and not in control rats.
I conclude that stress increases the NE modulation in VH, but not in DH, thus increasing the role of emotional processing associated with the VH.