Basal forebrain contributes to default mode network regulation

Abstract

The default mode network (DMN) is a collection of cortical brain regions that is active during states of rest or quiet wakefulness in humans and other mammalian species. A pertinent characteristic of the DMN is a suppression of local field potential gamma activity during cognitive task performance as well as during engagement with external sensory stimuli. Conversely, gamma activity is elevated in the DMN during rest. Here, we document that the rat basal forebrain (BF) exhibits the same pattern of responses, namely pronounced gamma oscillations during quiet wakefulness in the home cage and suppression of this activity during active exploration of an unfamiliar environment. We show that gamma oscillations are localized to the BF and that gamma-band activity in the BF has a directional influence on a hub of the rat DMN, the anterior cingulate cortex, during DMN-dominated brain states. The BF is well known as an ascending, activating, neuromodulatory system involved in wake-sleep regulation, memory formation, and regulation of sensory information processing. Our findings suggest a hitherto undocumented role of the BF as a subcortical node of the DMN, which we speculate may be important for switching between internally and externally directed brain states. We discuss potential BF projection circuits that could underlie its role in DMN regulation and highlight that certain BF nuclei may provide potential target regions for up- or down-regulation of DMN activity that might prove useful for treatment of DMN dysfunction in conditions such as epilepsy or major depressive disorder.

Keywords: anterior cingulate cortex; gamma suppression; granger causality.

Fig. 1.

Histology: A typical electrode penetration with coagulation mark. Recording sites were localized to the ventral pallidum and nucleus basalis regions of the basal forebrain. B, nucleus basalis; EAC, central extended amygdala; LPO, lateral preoptic nucleus; mfb, medial forebrain bundle; SIB, substantia innominata; VP, ventral pallidum.

Fig. 2.

Behavior analysis. (A) Schematic representation of the movement path during the behavioral conditions. Yellow circles represent objects. (B) Pie charts illustrating the occurrence of different behaviors in the three behavioral conditions.

Fig. 3.

BF gamma deactivation during arena exploration. (A) BF spectral power in the home cage and during arena exploration. f, frequency. (B) Movement-sensor values in quartiles plotted against gamma power for the home-cage and arena-exploration conditions. (C) Consistency of gamma power suppression over multiple days of arena exploration. HC, home cage. (D) Rapid switching of gamma power upon transfer to the home cage. The vertical line indicates the time of switching. (E) Single-session LFP spectrogram of BF activity in the arena and home cage. Bars above the spectrogram indicate epochs when exploratory locomotor behavior was interrupted by grooming (black bars) and quiet wakefulness (green bars). (F) Average BF gamma power for different behaviors (shaded areas represent SEM). f, frequency.

Fig. 4.

BF gamma deactivation during object exploration. (A) Average LFP gamma power during object and arena exploration compared with home cage (HC) values. f, frequency. (B) Single-session BF LFP spectrogram during object-exploration and home-cage conditions. Purple bars above the spectrogram represent epochs of object exploration. (C) Scatter plot of BF gamma activity during arena and object exploration plotted against home-cage values across individual recordings.

Fig. 5.

BF spiking activity couples to gamma oscillations. (A) Distribution of the best phase angle for each of our phase-locked neurons for both home-cage (HC) and arena (AR) conditions. (B–E) One sample neuron recorded in the home cage (Top Row) and in the arena (Bottom Row). (B) Probability of firing in a particular 14° bin over 10 bandpass filters for the LFP data. The PLI is shown at right and is the coefficient of variance over all angles for each band pass. f, frequency. (C) Spike times (red hash mark) on the LFP (black solid lines). (D) Polar histograms of the phase responses at each neuron’s best frequency and at the minimum and maximum band pass used. (E) Spike-triggered averages and autocorrelations (Insets) show 1,000 waveforms for each unit. The spiking and LFP recordings analyzed here were obtained from the same electrode.

Fig. 6.

Gamma oscillations in the ACC and VC and their functional interactions with the BF. (A) ACC and VC spectral LFP power for the arena-exploration and home-cage conditions. (Insets) Rapid switching of the ACC but not VC gamma upon transfer from the arena to the home cage. (B) BF–ACC and BF–VC spectral coherence. (C) Group mean of directional interactions between BF and cortical areas for home-cage and arena conditions. Insets show examples of detected BF gamma bursts used for the analyses. f, frequency. (D) Averaged directional interaction strength between BF and the ACC and VC cortical areas.