A functional topography within the cholinergic basal forebrain for processing sensory cues associated with reward and punishment

Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. The basal forebrain features distinct connectivity along its anteroposterior axis that could impart regional differences in feature processing. Here, we simultaneously measured bulk BFCN activity from an anterior structure, the horizontal limb of the diagonal band (HDB), and from the posterior tail of the basal forebrain in globus pallidus and substantia innominata (GP/SI) over a 30-day period as mice learned a sensory reversal task. Although HDB and GP/SI responses were similar for many features, HDB more closely tracked fluctuations in pupil-indexed brain state and exhibited stronger responses to reward omission than to delivery of anticipated awards. In GP/SI, BFCNs were strongly activated by sound, and this response was further enhanced for punishment-predicting – but not reward-predicting – cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.

Whole-Brain Map of Long-Range Monosynaptic Inputs to Different Cell Types in the Amygdala of the Mouse

The amygdala, which is involved in various behaviors and emotions, is reported to connect with the whole brain. However, the long-range inputs of distinct cell types have not yet been defined. Here, we used a retrograde trans-synaptic rabies virus to generate a whole-brain map of inputs to the main cell types in the mouse amygdala. We identified 37 individual regions that projected to neurons expressing vesicular glutamate transporter 2, 78 regions to parvalbumin-expressing neurons, 104 regions to neurons expressing protein kinase C-δ, and 89 regions to somatostatin-expressing neurons. The amygdala received massive projections from the isocortex and striatum. Several nuclei, such as the caudate-putamen and the CA1 field of the hippocampus, exhibited input preferences to different cell types in the amygdala. Notably, we identified several novel input areas, including the substantia innominata and zona incerta. These findings provide anatomical evidence to help understand the precise connections and diverse functions of the amygdala.

A Substantia Innominata-midbrain Circuit Controls a General Aggressive State

SUMMARYAnimals display various aggressive behaviors essential for survival, while ‘uncontrollable’ attacks and abnormal aggressive states have massive social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but whether there are circuits governing a general aggressive state to promote diverse aggressive behaviors remains unknown. Here, we found that posterior substantia innominata (pSI) neurons responded to multiple aggression-provoking cues with graded activity of differential dynamics, predicting the aggressive state and the topography of aggression in mice. Activation of pSI neurons projecting to the periaqueductal gray (PAG) increased aggressive arousal and robustly initiated/promoted all the types of aggressive behavior examined in an activity level-dependent manner. Inactivation of the pSI circuit largely blocked diverse aggressive behaviors, but not mating. By encoding a general aggressive state, the pSI-PAG circuit universally drives multiple aggressive behaviors and thus may provide a potential target for alleviating human pathological aggression.

The Cholinergic Multicompartmental Basal Forebrain Microcircuit

The basal forebrain (BF) is composed of an affiliation of structures, including the medial septum, ventral pallidum (VP), vertical diagonal band (VDB) and horizontal diagonal band (HDB) nuclei, substantia innominata/extended amygdala (SI/EA), and peripallidal regions. Together, they constitute one of the most extensive multicompartmental microcircuits in the brain. A prominent feature of the mammalian BF is the presence of aggregated and nonaggregated, large, cholinergic neurons, which project to the cerebral cortex, the hippocampal complex, and the amygdala. This highly complex system has been implicated in cortical activation, attention, motivation, and memory, as well as neuropsychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, and drug abuse. Advances in modern tracing, genetic, and refined pharmacological techniques have dramatically increased the understanding of how the BF cholinergic system can support both phasic acetylcholine (ACh) release in attention, memory, and sensory processing and tonic ACh release over broad cortical areas as part of a general arousal effect.