The menagerie of the basal forebrain: how many (neural) species are there, what do they look like, how do they behave and who talks to whom?

Highlights

• Cholinergic, GABA and glutamatergic neurons all affect cortical activation.

• Cholinergic neurons suppress cortical delta activity and promote cortical plasticity.

• GABA/parvalbumin neurons promote gamma activity and fast arousals from sleep.

• GABA/somatostatin neurons inhibit wake-promoting neurons.

• Increases in extracellular adenosine promote sleep during prolonged wakefulness.

The diverse cell-types of the basal forebrain control sleep–wake states, cortical activity and reward processing. Large, slow-firing, cholinergic neurons suppress cortical delta activity and promote cortical plasticity in response to reinforcers. Large, fast-firing, cortically-projecting GABAergic neurons promote wakefulness and fast cortical activity. In particular, parvalbumin/GABAergic neurons promote neocortical gamma band activity. Conversely, excitation of slower-firing somatostatin/GABAergic neurons promotes sleep through inhibition of cortically-projecting neurons. Activation of glutamatergic neurons promotes wakefulness, likely by exciting other cortically-projecting neurons. Similarly, cholinergic neurons indirectly promote wakefulness by excitation of wake-promoting, cortically-projecting GABAergic neurons and/or inhibition of sleep-promoting somatostatin/GABAergic neurons. Both glia and neurons increase the levels of adenosine during prolonged wakefulness. Adenosine presynaptically inhibits glutamatergic inputs to wake-promoting cholinergic and GABAergic/parvalbumin neurons, promoting sleep.

Introduction

The basal forebrain (BF) is a large heterogeneous structure located close to the ventral surface of the rostral telencephalon (Figure 1) which is involved in sleep–wake control, attention and reward processing [1, 2, 3]. Until relatively recently, most of these functions were ascribed to the BF cholinergic neurons which degenerate in Alzheimer’s disease and other dementias [4]. However, recent technical advances which allowed the specific targeting of GABAergic and glutamatergic BF neurons have revealed important roles for these neurons and have refined our understanding of cholinergic neurons [2]. Thus, in this review we summarize our current knowledge of these different neural species within the BF menagerie. We discuss their cellular properties (what they look like), their functions (how they behave) and how they interact (who talks to whom). We focus on the intermediate/caudal part of BF which contains neurons projecting to the neocortex (Figure 1) and on studies conducted in mice, since recent optogenetic and chemogenetic studies have used this species.