Subpopulations of somatostatin-immunoreactive non-pyramidal neurons in the amygdala and adjacent external capsule project to the basal forebrain: evidence for the existence of GABAergic projection neurons in the cortical nuclei and basolateral nuclear complex

Abstract

The hippocampus and amygdala are key structures of the limbic system whose connections include reciprocal interactions with the basal forebrain (BF). The hippocampus receives both cholinergic and GABAergic afferents from the medial septal area of the BF. Hippocampal projections back to the medial septal area arise from non-pyramidal GABAergic neurons that express somatostatin (SOM), calbindin (CB), and neuropeptide Y (NPY). Recent experiments in our lab have demonstrated that the basolateral amygdala, like the hippocampus, receives both cholinergic and GABAergic afferents from the BF. These projections arise from neurons in the substantia innominata (SI) and ventral pallidum (VP). It remained to be determined, however, whether the amygdala has projections back to the BF that arise from GABAergic non-pyramidal neurons. This question was investigated in the present study by combining Fluorogold (FG) retrograde tract tracing with immunohistochemistry for GABAergic non-pyramidal cell markers, including SOM, CB, NPY, parvalbumin, calretinin, and glutamic acid decarboxylase (GAD). FG injections into the BF produced a diffuse array of retrogradely labeled neurons in many nuclei of the amygdala. The great majority of amygdalar FG+ neurons did not express non-pyramidal cell markers. However, a subpopulation of non-pyramidal SOM+ neurons, termed “long-range non-pyramidal neurons” (LRNP neurons), in the external capsule, basolateral amygdala, and cortical and medial amygdalar nuclei were FG+. About one-third of the SOM+ LRNP neurons were CB+ or NPY+, and one-half were GAD+. It remains to be determined if these inhibitory amygdalar projections to the BF, like those from the hippocampus, are important for regulating synchronous oscillations in the amygdalar-BF network.

The densities of calbindin and parvalbumin, but not calretinin neurons, are sexually dimorphic in the amygdala of the guinea pig

“…However, it is worth emphasizing here that not all CBþ neurons in the amygdala have the morphology of interneurons (present results and Kemppainen and Pitkänen, 2000) and not all of them are GABAþ (Kemppainen and Pitkänen, 2000). Moreover, there is a direct evidence that some CBþ neurons are projecting neurons (Moryś et al, 1999;McDonald et al, 2012). The next important fact is that both, CBþ (present study) and GABAþ (Stefanova, 1998) neurons are in the amygdala sexually dimorphic as they are also in several other brain regions Orikasa and Sakuma, 2010;Yahr, 2011).…”

Decreased Numbers of Somatostatin-Expressing Neurons in the Amygdala of Subjects With Bipolar Disorder or Schizophrenia: Relationship to Circadian Rhythms

“…Predominant SST-IR neuron decreases in the LN, known to mediate plasticity and rapid behavioral responses to fearful stimuli (86, 87) , point to abnormal processing of sensory stimuli and fear response. In addition, it is possible that small populations of LN SST-IR neurons projecting to the entorhinal cortex (88), and BN and CO SST-IR neurons to the basal forebrain (89) may be involved, potentially contributing to disrupted sensory gating in SZ (90–94), and dysregulation of sleep-wake patterns in BD (95–97) through the basal forebrain (98, 99), respectively.…”

Amygdala Microcircuits Controlling Learned Fear

“… 1 Although the vast majority of GABAergic neurons in the BLA are local-circuit cells, a recent study reported that a small subset of SOM + neurons located in or near the external capsule projects to the basal forebrain (McDonald et al, 2012). …”