β‐adrenergic receptors are differentially expressed in distinct interneuron subtypes in the rat hippocampus

Abstract

Noradrenaline (NA) acting via ␤-adrenergic receptors (␤ARs) plays an important role in the modulation of memory in the hippocampus. ␤ARs have been shown to be expressed in principal cells, but their distribution across different interneuron classes is unknown. We have used specific interneuron markers including calcium binding proteins (parvalbumin, calbindin, and calretinin) and neuropeptides (somatostatin, neuropeptide Y, and cholecystokinin) together with either ␤1AR or ␤2AR to determine the distribution of these receptors in all major subfields of the hippocampus. We found that ␤1AR-expressing interneurons were more prevalent in the CA3 and CA1 regions of the hippocampus than in the dentate gyrus, where they were relatively sparse. ␤2AR-expressing interneurons were more uniformly distributed between all three regions of the hippocampus. A high proportion of neuropeptide Y-containing interneurons in the dentate gyrus co-expressed ␤2AR. ␤1AR labeling was common in interneurons expressing somatostatin and parvalbumin in the CA3 and CA1 regions, particularly in the stratum oriens of these regions. ␤2AR labeling was more likely to be found than ␤1AR labeling in cholecystokinin-expressing interneurons. In contrast, calretinin-containing interneurons were virtually devoid of ␤1AR or ␤2AR labeling. These regional and interneuron type-specific differences suggest functionally distinct roles for NA in modulating hippocampal activity via activation of ␤ARs.

β-Adrenergic modulation of spontaneous spatiotemporal activity patterns and synchrony in hyperexcitable hippocampal circuits

“…High-frequency oscillations observed in human and animals are thought to play key roles in fast epileptiform network synchronization (Huberfeld et al 2011). The underlying changes in spectral bands observed here could also be indicative of the heightened or dampened activity in distinct cell subpopulations (Cox et al 2008). It is important to add that in the 4-AP model of developing mouse tissue, ionotropic glutamate or GABA receptor blockade resulted in significant alterations of spontaneous burst propagation patterns measured electrically (Gonzalez-Sulser et al 2011).…”

“…Although not a sole effect, VNS in patients and in animals elevates levels of norepinephrine (NE) in the brain. This additional NE is thought to be anticonvulsive (Giorgi et al 2004;Krahl et al 1998;Roosevelt et al 2006;Szot et al 1999Szot et al , 2001Weinshenker and Szot 2002).In the brain, noradrenergic fibers densely innervate polymorphic hippocampal, neocortical, and cerebellar tissues (Cox et al 2008;Giorgi et al 2004;Grant and Redmond 1981;Milner et al 2000;Weinshenker and Szot 2002). Actions of NE are mediated by ␣-adrenergic (␣-AR) and ␤-adrenergic receptors (␤-AR) and their respective subtypes (Mueller and Dunwiddie 1983;Mueller et al 1981Mueller et al , 1982Weinshenker and Szot 2002).…”

“…In the brain, noradrenergic fibers densely innervate polymorphic hippocampal, neocortical, and cerebellar tissues (Cox et al 2008;Giorgi et al 2004;Grant and Redmond 1981;Milner et al 2000;Weinshenker and Szot 2002). Actions of NE are mediated by ␣-adrenergic (␣-AR) and ␤-adrenergic receptors (␤-AR) and their respective subtypes (Mueller and Dunwiddie 1983;Mueller et al 1981Mueller et al , 1982Weinshenker and Szot 2002).…”

β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus

“…Hippocampal pyramidal cells and dentate gyrus granule cells express all four receptor subtypes (Nicholas et al 1993;Hillman et al 2005;Guo and Li 2007). Interneurons also express a1-and b-adrenergic receptors (b-ARs), although there are substantial differences in levels of expression of b1 and b2 receptors in different types of interneurons (Papay et al 2006;Cox et al 2008). The a adrenergic receptors are coupled to Gq or Gi type G proteins and appear to have a role in both memory and synaptic plasticity in some brain regions (for reviews, see Tully and Bolshakov 2010).…”

Norepinephrine triggers metaplasticity of LTP by increasing translation of specific mRNAs

“…One potential contributing factor is the spatial location of b-ARs on hippocampal neurons in CA1. b-ARs are found in all principal cell layers in the hippocampus, including area CA1 (Hillman et al 2005;Guo and Li 2007;Cox et al 2008). A concentration of distally situated dendritic b-ARs could, hypothetically, require some lag time to relay synaptic signals to the nucleus of pyramidal neurons.…”