Basal forebrain innervation of the amygdala: an anatomical and computational exploration

Theta oscillations of the mammalian amygdala are associated with processing, encoding and retrieval of aversive memories. In the hippocampus, the power of the network theta oscillation is modulated by basal forebrain (BF) GABAergic projections. Here, we combine anatomical and computational approaches to investigate if similar BF projections to the amygdaloid complex provide an analogous modulation of local network activity. We used retrograde tracing with fluorescent immunohistochemistry to identify cholinergic and non-cholinergic parvalbumin- or calbindin-immunoreactive BF neuronal subgroups targeting the input (lateral and basolateral nuclei) and output (central nucleus and the central bed nucleus of the stria terminalis) regions of the amygdaloid complex. We observed a dense non-cholinergic, putative GABAergic projection from the ventral pallidum (VP) and the substantia innominata (SI) to the basolateral amygdala (BLA). The VP/SI axonal projections to the BLA were confirmed using viral anterograde tracing and transsynaptic labeling. We tested the potential function of this VP/SI-BLA pathway in a 1000-cell biophysically realistic network model, which incorporated principal neurons and three major interneuron groups of the BLA, together with extrinsic glutamatergic, cholinergic, and VP/SI GABAergic inputs. We observed in silico that theta-modulation of VP/SI GABAergic projections enhanced theta oscillations in the BLA via their selective innervation of the parvalbumin-expressing local interneurons. Ablation of parvalbumin-, but not somatostatin- or calretinin-expressing, interneurons reduced theta power in the BLA model. These results suggest that long-range BF GABAergic projections may modulate network activity at their target regions through the formation of a common interneuron-type and oscillatory phase-specific disinhibitory motif.