Abstract
The subiculum (SUB) is a pivotal structure positioned between the hippocampus proper and various cortical and subcortical areas. Despite the growing body of anatomical and intrinsic electrophysiological data of subicular neurons, modulation of synaptic transmission in the SUB is not well understood. In the present study we investigated the role of group II metabotropic glutamate receptors (mGluRs), which have been shown to be involved in the regulation of synaptic transmission by suppressing presynaptic cAMP activity. Using field potential and patch-clamp whole cell recordings we demonstrate that glutamatergic transmission at CA1-SUB synapses is depressed by group II mGluRs in a cell-type specific manner. Application of the group II mGluR agonist (2S,1′R,2′R,3′R)-2-(2, 3-dicarboxycyclopropyl)glycine (DCG-IV) led to a significantly higher reduction of excitatory postsynaptic currents in subicular bursting cells than in regular firing cells. We further used low-frequency stimulation protocols and brief high-frequency bursts to test whether synaptically released glutamate is capable of activating presynaptic mGluRs. However, neither frequency facilitation is enhanced in the presence of the group II mGluR antagonist LY341495, nor is a test stimulus given after a high-frequency burst. In summary, we present pharmacological evidence for presynaptic group II mGluRs targeting subicular bursting cells, but both low- and high-frequency stimulation protocols failed to activate presynaptically located mGluRs.
Highlights
The subiculum (SUB) is the main output region of the hippocampal formation and functions as the major interface between the hippocampus proper and various cortical and subcortical regions
We examined the effects of the specific group II metabotropic glutamate receptors (mGluRs) agonists, (2S,19S,29S)-2-(2-carboxycyclopropyl)glycine (L-CCG-1) and (2S,19R,29R,39R)-2-(2, 3-dicarboxycyclopropyl)glycine (DCG-IV), in the SUB and compared these findings with the application of these drugs in areas CA1 and CA3
We have shown that excitatory synaptic transmission at CA1-SUB synapses can be modulated by a group II mGluR agonist in a target-cell specific manner
Summary
The subiculum (SUB) is the main output region of the hippocampal formation and functions as the major interface between the hippocampus proper and various cortical and subcortical regions. Metabotropic glutamate receptors (mGluRs) have important roles in regulating synaptic transmission [9] by providing a negative feedback of glutamatergic transmission at central neurons [10,11,12,13]. Pharmacological activation of mGluRs provides a treatment option for hyperexcitability disorders as epilepsy or schizophrenia [14,15]. We examined the effects of the specific group II mGluR agonists, (2S,19S,29S)-2-(2-carboxycyclopropyl)glycine (L-CCG-1) and (2S,19R,29R,39R)-2-(2, 3-dicarboxycyclopropyl)glycine (DCG-IV), in the SUB and compared these findings with the application of these drugs in areas CA1 and CA3. We show that group II mGluRs activation differently affects synaptic transmission in these three different brain regions of the hippocampal formation. At CA1-SUB synapses excitatory postsynaptic responses are reduced in the presence of the mGluR agonists in a target-specific manner
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