Subcallosal area 25: Its responsivity to the stress hormone cortisol and its opposing effects on appetitive motivation in marmosets.

Aberrant activity in caudal subcallosal anterior cingulate cortex (scACC) is implicated in depression and anxiety symptomatology, with its normalisation a putative biomarker of successful treatment response. The function of scACC in emotion processing and mental health is not fully understood despite its known influence on stress-mediated processes through its rich expression of mineralocorticoid and glucocorticoid receptors. Here we examine the causal interaction between area 25 within scACC (scACC-25) and the stress hormone, cortisol, in the context of anhedonia and anxiety-like behaviour. In addition, the overall role of scACC-25 in hedonic capacity and motivation is investigated under transient pharmacological inactivation and overactivation. The results suggest that a local increase of cortisol in scACC-25 shows a rapid induction of anticipatory anhedonia and increased responsiveness to uncertain threat. Separate inactivation and overactivation of scACC-25 increased and decreased motivation and hedonic capacity, respectively, likely through different underlying mechanisms. Together, these data show that area scACC-25 has a causal role in consummatory and motivational behaviour and produces rapid responses to the stress hormone cortisol, that mediates anhedonia and anxiety-like behaviour.

Quantifying anhedonia-like symptoms in marmosets using appetitive Pavlovian conditioning.

Blunted reward responsivity is associated with anhedonia in humans and is a core feature of depression. This protocol describes how to train the common marmoset, Callithrix jacchus, on an appetitive Pavlovian conditioning paradigm to measure behavioral and cardiovascular correlates of anticipatory and consummatory phases of reward processing. We describe how to use intracerebral infusions to manipulate brain regions whose activity is relevant to impaired reward processing in depression and how the paradigm can be used to test antidepressant efficacy. For complete details on the use and execution of this protocol, please refer to Alexander et al. (2019).

GABA, noise and gain in human visual cortex.

High levels of GABA (gamma-aminobutyric acid, the brain's primary inhibitory neurotransmitter) are associated with enhanced cognitive and perceptual performance. It has been proposed that these effects result from GABA reducing neural noise or variability, but the precise mechanisms remain unknown. We have measured how individual differences in GABA concentration in the visual cortex are related to performance on a visual contrast discrimination task. Our results reveal that the facilitatory strength of the typical "dipper" function elicited by this task is strongly correlated with GABA concentration. A simple, biologically plausible, network model comprising excitatory and suppressive neural populations accounts for the data well and indicates that the strength of suppression increases as GABA concentration increases. Inter-individual variations in GABA were correlated both with the inhibition strength of the model (mimicking the effect of GABA) and, inversely, with the magnitude of the response criterion. This enhanced suppression has the dual effect of suppressing noise and reducing the gain of the neural response. Our findings thus suggest that the changes in performance conferred by high GABA concentration are mediated by both a reduction of noise and, paradoxically, a reduction in neural, but not perceptual, sensitivity.