Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

Abstract

The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium-binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67-GFP knock-in mice) or PV+ neurons (PV-Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67-GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 μm) or medium-sized (15–20 μm) GFP+ neurons. Most medium and large-sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast-firing and spontaneously active in vitro. They exhibited prominent hyperpolarization-activated inward currents and subthreshold “spikelets,” suggestive of electrical coupling. PV+ neurons recorded in PV-Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep.

Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations

“…We have identified, for the first time to our knowledge, a specific cell type (PV neurons) important in the BF control of cortical GBO. Because most BF PV neurons are GABAergic (21,22), our results are surprising in indicating that this presumptively inhibitory input controls cortical activation, likely by synchronizing the activity of cortical inhibitory neurons. Furthermore, we identified a frequency-specific cortical response to a subcortical stimulation, suggesting that the cortex contains an endogenous oscillator tuned preferentially to GBO frequencies.…”

“…One possible caveat is that optogenetic stimulation may cause an unphysiologically synchronous activation of the target neuronal population. However, our recent in vitro data (21) suggest that BF GABAergic/PV neurons are electrically coupled; thus our nearly synchronous optogenetic stimulation of a subset of these neurons may parallel synchronous firing of a subset of these neurons in vivo. In fact, one group of neurochemically unidentified noncholinergic BF neurons recorded in vivo exhibited synchronous firing in response to salient stimuli, correlated with a local field potential recorded in the frontal cortex (36).…”

“…Cortical EEG recordings, immunohistochemistry, and in vitro recordings were performed as described previously (21,41,44). Details of the experimental procedures are provided in SI Materials and Methods.…”

“…Many cortically projecting BF GABAergic neurons contain the calcium-binding protein PV, and a large majority of BF PV neurons are GABAergic (21,22). Recordings from identified BF PV neurons in anesthetized animals revealed they increase their discharge rate during cortical activation induced by sensory stimulation (23).…”

Gamma band directional interactions between basal forebrain and visual cortex during wake and sleep states

“…The high gamma power in BF compared to cortex is unexpected, given that a regular geometric arrangement of dendrites is thought to be one of the most important factors contributing to LFP amplitude and that such an arrangement is certainly less prevalent in BF than in the cortex. One factor contributing to the prominent BF gamma oscillations may be the presence of gap junctions, which have been reported in BF populations (McKenna et al, 2013) and which can synchronize temporal neural activity (Gibson et al, 1999;Deans et al, 2001), thus enhancing the overall LFP amplitude. Certain membrane characteristics, by which neurons can generate intrinsic gamma oscillations (Garcia-Rill et al, 2014) without the need of excitatory-inhibitory coupling, could also be at work in BF to generate the observed large gamma power.…”