alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis.

Shields AD, Wang Q, Winder DG
Neuroscience. 2009 163 (1): 339-51

PMID: 19527774 · PMCID: PMC2744292 · DOI:10.1016/j.neuroscience.2009.06.022

Stress is a major driving force in reinstatement of drug-seeking behavior. The bed nucleus of the stria terminalis (BNST) has been identified as a key brain region in this behavior, and receives a dense input of the stress-neurotransmitter norepinephrine through the ventral noradrenergic bundle. Activation of alpha(2)-adrenergic receptors (alpha(2)-ARs) in the BNST blocks stress-induced reinstatement of drug-seeking, indicating a potentially important role for these receptors. Currently, it is unclear how alpha(2)-AR agonists elicit this behavioral action, or through which alpha(2)-AR subtype. Activation of alpha(2)-ARs decreases glutamatergic transmission in the BNST, an effect which is nearly absent in the alpha(2A)-AR knockout mouse. Here, we take advantage of a knock-in mouse in which a hemagglutinin-tagged alpha(2A)-AR was inserted into the endogenous locus, along with the alpha(2A)-AR selective agonist guanfacine, to further study the role of the alpha(2A)-AR subtype in modulation of neurotransmission in the BNST. Using immunohistochemistry, we find that alpha(2A)-ARs are highly expressed in the BNST, and that this expression is more similar in distribution to the vesicular glutamate transporters than to either norepinephrine transporter or tyrosine hydroxylase positive terminals. Using whole cell patch-clamp recordings, we show that guanfacine causes a depression of evoked excitatory and, to a more limited extent, inhibitory fast synaptic transmission. In total, these data support a prominent heterosynaptic role for alpha(2A)-ARs in modulating fast synaptic transmission in the BNST.

MeSH Terms (21)

Adrenergic alpha-Agonists Animals Excitatory Postsynaptic Potentials Gene Knock-In Techniques Glutamic Acid Guanfacine Inhibitory Postsynaptic Potentials Male Mice Mice, Inbred C57BL Mice, Knockout Neurons Norepinephrine Organ Culture Techniques Patch-Clamp Techniques Receptors, Adrenergic, alpha-2 Septal Nuclei Stress, Psychological Substance-Related Disorders Synaptic Transmission Time Factors

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