D₁‐like dopamine receptors selectively block P/Q‐type calcium channels to reduce glutamate release onto cholinergic basal forebrain neurones of immature rats

Abstract

Basal forebrain (BF) nuclei, consisting of the vertical and horizontal limbs of diagonal band of Broca (HDBB), substantia innominata (SI) and nucleus of basalis (nB), form the principal source of cholinergic innervation to the cortical and subcortical brain regions (Rye et al. 1984). Pathologically, degeneration of these cholinergic neurones has been observed in patients with Alzheimer's disease (Coyle et al. 1983;Oyanagi et al. 1989). Morphological studies have shown that the BF region receives dopaminergic fibres from the ventral tegmental area, substantia nigra pars compacta and medial zona interna (Martinez-Murillo et al. 1988;Semba et al. 1988;Eaton et al. 1994). It has been electrophysiologically demonstrated that activation of presynaptic dopamine D 1 -like receptors reduces glutamate release onto magnocellular BF neurones, mainly cholinergic, in a calcium-dependent manner (Momiyama et al. 1996). Although multiple types of Ca 2+ channels including N-, P/Q-and R-type channels are involved in the fast synaptic transmission in the central nervous system (Luebke et al. 1993;Takahashi & Momiyama, 1993;Regehr & Mintz, 1994;Umemiya & Berger, 1994;Wheeler et al. 1994;Wu & Saggau, 1994;Wu et al. 1998), it remains to be elucidated whether activation of these D 1 -like receptors blocks specific subtypes of Ca 2+ channels. The aim of the present study is to identify which Ca 2+ -channel subtypes are involved in the D 1 -like receptor-mediated presynaptic inhibition of the non-NMDA glutamatergic transmission onto BF cholinergic neurones. In the present study, cholinergic BF neurones could be pre-labelled using Cy3-192IgG (Wu et al. 2000), a marker for p75 neurotrophic factor receptors (Hartig et al. 1998), as neurones

Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons

“…The glutamate release at these synapses is controlled by multiple types of presynaptic Ca 2ϩ channels (P/Q-and Ntypes), and these channels undergo postnatal developmental changes in which the contribution of the P/Q-type increases with age at the expense of the N-type Ca 2ϩ channels (Momiyama 2010; Momiyama and Fukazawa 2007; Sim and Griffith 1996). Furthermore, the glutamatergic transmission to the BF cholinergic neurons has been shown to be inhibited by muscarinic M 2 , dopamine D 1 , and somatostatin SST 1/4 presynaptic receptors, but unlike dopamine and somatostatin, which only act presynaptically, acetylcholine and adenosine, as shown in the present study, have both pre-and postsynaptic effects (Arrigoni et al 2006;Momiyama 2010;Momiyama and Fukazawa 2007;Momiyama and Zaborszky 2006;Sim and Griffith 1996).…”

Amyloid β Protein Modulates Glutamate-Mediated Neurotransmission in the Rat Basal Forebrain: Involvement of Presynaptic Neuronal Nicotinic Acetylcholine and Metabotropic Glutamate Receptors

“…mEPSCs recorded from the neurons, held at a membrane potential of Ϫ60 mV, were mediated by the AMPA and kainate subtypes of glutamate receptors because application of CNQX, an AMPA/kainate receptor antagonist, completely abolished such events. Although evoked glutamatergic EPSCs have been recorded in the DBB, such reports are infrequent (Easaw et al, 1997;Momiyama and Fukazawa, 2007). In part, this is related to geometrical considerations in coronal and horizontal forebrain slices, which do not optimally preserve glutamate afferents (originating from prefrontal cortex and other sources) to the DBB and thus make electrical stimulation-evoked EPSCs difficult (Jhamandas and Bourque, 2000).…”

Amyloid β Oligomers (Aβ1–42Globulomer) Suppress Spontaneous Synaptic Activity by Inhibition of P/Q-Type Calcium Currents

“…Certain pathways that are critically involved in the dementia symptoms of AD depend on intact P/Q channel-mediated calcium signaling, and a general decrease in the transmitter release in such pathways may be detrimental to cognitive function. For example, Momiyama and Fukazawa (2007) could show that P/Qtype calcium channels facilitate glutamate release onto cholinergic basal forebrain neurons, thereby altering cholinergic transmission. A suppression of P/Q-type calcium currents may therefore result in modified cortical acetylcholine levels.…”