Abstract
Dopamine D2-like receptors (D2R) play an important role in the regulation of hippocampal neuronal excitability and contribute to the regulation of synaptic plasticity, the encoding of hippocampus-dependent memories and the regulation of affective state. In line with this, D2R are targeted in the treatment of psychosis and affective disorders. It has been proposed that the dorso-ventral axis of the hippocampus can be functionally delineated into the dorsal pole that predominantly processes spatial information and the ventral pole that mainly addresses hippocampal processing of emotional and affective state. Although dopaminergic control of hippocampal information processing has been the focus of a multitude of studies, very little is known about the precise distribution of D2R both within anatomically defined sublayers of the hippocampus and along its dorsoventral axis, that could in turn yield insights as to the functional significance of this receptor in supporting hippocampal processing of spatial and affective information. Here, we used an immunohistochemical approach to precisely scrutinize the protein expression of D2R both within the cellular and dendritic layers of the hippocampal subfields, and along the dorso-ventral hippocampal axis. In general, we detected significantly higher levels of protein expression of D2R in the ventral, compared to the dorsal poles with regard to the CA1, CA2, CA3 and dentate gyrus (DG) regions. Effects were very consistent: the molecular layer, granule cell layer and polymorphic layer of the DG exhibited higher D2R levels in the ventral compared to dorsal hippocampus. D2R levels were also significantly higher in the ventral Stratum oriens, Stratum radiatum, and Stratum lacunosum-moleculare layers of the CA1 and CA3 regions. The apical dendrites of the ventral CA2 region also exhibited higher D2R expression compared to the dorsal pole. Taken together, our study suggests that the higher D2R expression levels of the ventral hippocampus may contribute to reported gradients in the degree of expression of synaptic plasticity along the dorso-ventral hippocampal axis, and may support behavioral information processing by the ventral hippocampus.
Highlights
Synaptic plasticity and memory formation in the hippocampus, in their essence, are dependent on excitatory glutamatergic transmission (Citri and Malenka, 2008; Lisman, 2017)
In order to better understand the functional differences across the hippocampal longitudinal axis, we examined the protein levels of D2-like receptors (D2R) in the dentate gyrus (DG), CA3, CA2 and CA1 regions of the rat dorsal, intermediate and ventral hippocampus by immunohistochemical staining
The dorsal DG exhibited the lowest levels of D2R compared to expression levels in the ventral hippocampus
Summary
Synaptic plasticity and memory formation in the hippocampus, in their essence, are dependent on excitatory glutamatergic transmission (Citri and Malenka, 2008; Lisman, 2017). Various neurotransmitter systems exert a modulatory role, thereby influencing the direction of change (Kemp and Manahan-Vaughan, 2005), effectiveness (Hansen and ManahanVaughan, 2015), duration (Twarkowski and Manahan-Vaughan, 2016) or robustness (Manahan-Vaughan and Kulla, 2003) of synaptic strength, and learning and memory. D2 receptors modulate the beta-arrestin/GSK3 pathway and can alter the excitability of hippocampal mossy cells through this mechanism (Etter and Krezel, 2014). Both classes of dopamine receptors are postsynaptically expressed on dopamine-receptive cells (Rankin et al, 2009). In-depth knowledge about the spatial expression pattern of D2R would be beneficial for understanding the physiological role, and, the pathological role of this receptor
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