Morphological characterization of electrophysiologically and immunohistochemically identified basal forebrain cholinergic and neuropeptide Y-containing neurons

Abstract

The basal forebrain (BF) contains cholinergic as well as different types of non-cholinergic corticopetal neurons and interneurons, including neuropeptide Y (NPY) containing cells. BF corticopetal neurons constitute an extrathalamic route to the cortex and their activity is associated with an increase in cortical release of the neurotransmitter acetylcholine, concomitant with low voltage fast cortical EEG activity. It has been shown in previous studies (Duque et al. in J Neurophysiol 84:1627-1635, 2000) that in anesthetized rats BF cholinergic neurons fire mostly during low voltage fast cortical EEG epochs, while increased NPY neuronal firing is accompanied by cortical slow waves. In this paper, electrophysiologically and neurochemically characterized cholinergic and NPY-containing neurons were 3D reconstructed from serial sections and morphometrically analyzed. Cholinergic and NPY-containing neurons, although having roughly the same dendritic surface areas and lengths, were found to differ in dendritic thickness and branching structure. They also have distinct patterns of dendritic endings. The subtle differences in dendritic arborization pattern may have an impact on how synaptic integration takes place in these functionally distinct neuronal populations. Cholinergic neurons exhibited cortically projecting axons and extensive local axon collaterals. Elaborate local axonal arbors confined to the BF also originated from NPY-containing neurons. The presence of local axon collaterals in both cholinergic and NPY neurons indicates that the BF is not a mere conduit for various brainstem inputs to the cortex, but a site where substantial local processing must take place.

Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study

“…Furthermore, optogenetic studies using both gainand loss-of-function experiments provided compelling evidence that BF GABAergic/PV neurons control cortical fast activity typical of wakefulness (Kim et al, 2015). Cholinergic terminals from local collaterals and brainstem cholinergic neurons are located in close proximity of BF non-cholinergic neurons (Martinez-Murillo et al, 1990; Zaborszky and Duque, 2000; Duque et al, 2007). Specifically, cholinergic fiber varicosities appose GABAergic/PV neurons in BF .…”

“…However, the attribution of effects of optogenetic stimulation on behavior to activation of particular neurotransmitter systems and release of that neurotransmitter in target areas is not as simple as it first seems. Many neuromodulatory systems with long projecting axons also release neurotransmitter(s) locally through somatodendritic release (Adell and Artigas, 2004) or through activation of local axon collaterals (Duque et al, 2007;. Thus, the behavioral effects of "selective" optogenetic stimulation may be mediated not through release of neurotransmitter in distal targets but rather due to activation or inhibition of neighboring neurons.…”

Neuropeptide Y and posttraumatic stress disorder

“…NPY-containing neurons in the basal forebrain (BF) are slow-wave sleep-active cells. 111 In humans, NPY has been shown to have consistent sleep-promoting effects following intravenous administration, 65,112 particularly a decreased latency to onset of sleep. Given the low CNS NPY in PTSD patients, 113 the regulatory influence of NPY on noradrenergic systems, the noradrenergic 'overdrive' of patients with PTSD and the salutary effects of the alpha-1 noradrenergic receptor antagonist prazosin on sleep in this population, 114 it is possible that reduced NPY in PTSD subjects could contribute to the sleep abnormalities characteristically experienced by these patients.…”

Nitric oxide modulates the discharge rate of basal forebrain neurons

“…Predominant proportion of stimulus-off neurons were GABA-ergic (Manns et al 2000a, b), while only about 11% of stimulus-off neurons were non-GABA-ergic (Manns et al 2000b). These could, for example, contain neuropeptide Y (Duque et al 2000(Duque et al , 2007. Neurons that did not respond significantly or consistently were characterized as stimulusnon-identified.…”