Calcium Imaging of Basal Forebrain Activity during Innate and Learned Behaviors

Abstract

The basal forebrain (BF) plays crucial roles in arousal, attention, and memory, and its impairment is associated with a variety of cognitive deficits. The BF consists of cholinergic, GABAergic, and glutamatergic neurons. Electrical or optogenetic stimulation of BF cholinergic neurons enhances cortical processing and behavioral performance, but the natural activity of these cells during behavior is only beginning to be characterized. Even less is known about GABAergic and glutamatergic neurons. Here, we performed microendoscopic calcium imaging of BF neurons as mice engaged in spontaneous behaviors in their home cages (innate) or performed a go/no-go auditory discrimination task (learned). Cholinergic neurons were consistently excited during movement, including running and licking, but GABAergic and glutamatergic neurons exhibited diverse responses. All cell types were activated by overt punishment, either inside or outside of the discrimination task. These findings reveal functional similarities and distinctions between BF cell types during both spontaneous and task-related behaviors.

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?

“…Furthermore, they discharge with bursts of action potentials during states associated with EEG theta activity. Behavioral studies revealed a rapid response to reinforcers [32,33]. Cholinergic signals in the cortex promote cortical activation [34], facilitate fast and dynamic plasticity of sensory perception [35], enhance the salience of stimuli [36] and promote long-lasting synaptic plasticity [37].…”

The Input-Output Relationship of the Cholinergic Basal Forebrain

“…Towards this end we suggest two, not mutually-exclusive principles: 1) segregated inputs to the BFc convey specific cognitive operations and overlapping, common inputs mediate state-related changes; alternatively, 2) the complex set of inputs described in our study reflect multiple inbuilt templates for flexible control of cortical states in a modality-specific fashion via the tonic and phasic firing of cholinergic neurons (Hangya et al, 2015; Harrison et al, 2016). …”

“…However, recent studies suggest a more complex scenario that is characterized by a continuum of states rather than sharp transitions and, both in SWS and waking, finer distinctions can be made in terms of internal cortical dynamics and responsiveness to external stimuli (Harris and Thiele, 2011; McGinley et al, 2015; Vyazovskiy et al, 2011). The mechanism of how cortical arousal, movement-related activity (Harrison et al, 2016) and pupil micro-dilations (McGinley et al, 2015) are linked remains unexplained.…”

Pupil Dynamics Reflect Behavioral Choice and Learning in a Go/NoGo Tactile Decision-Making Task in Mice

“…Prominent theories are based on evidence suggesting that pupil diameter tracks changes in the activity of noradrenergic LC neurons in humans and non-human primates (Aston-Jones and Cohen, 2005; Gilzenrat et al, 2010; Murphy et al, 2014a; Varazzani et al, 2015). Behavioral arousal is closely related to LC activity (Samuels and Szabadi, 2008a; Carter et al, 2010; Sara and Bouret, 2012) and pupil dilation in mice (Reimer et al, 2014; McGinley et al, 2015b; Vinck et al, 2015), as well as other neuromodulatory systems including acetylcholine (ACh; Eggermann et al, 2014; Lin et al, 2015; Harrison et al, 2016). Therefore, the task-related pupil dilations that we report are likely correlated with activation of pupil-linked neuromodulator systems, including LC neuron activity, but this remains to be tested by directly recording LC neurons in mice.…”