Disentangling the effects of novelty, valence and trait anxiety in the bed nucleus of the stria terminalis, amygdala and hippocampus with high resolution 7T fMRI

Abstract Relative to the centromedial amygdala (CM), the bed nucleus of the stria terminalis (BNST) may exhibit more sustained activation toward threat, sensitivity to unpredictability and activation during anxious anticipation. These factors are often intertwined. For example, greater BNST (vs CM) activation during a block of aversive stimuli may reflect either more sustained activation to the stimuli or greater activation due to the anticipation of upcoming stimuli. To further investigate these questions, we had participants (19 females, 9 males) complete a task adapted from a study conducted by Somerville, Whalen and Kelly in 2013, during high-resolution 7-Tesla fMRI BOLD acquisition. We found a larger response to negative vs neutral blocks (sustained threat) than to images (transient) in the BNST, but not the CM. However, in an additional analysis, we also found BNST, but not CM, activation to the onset of the anticipation period on negative vs neutral trials, possibly contributing to BNST activation across negative blocks. Predictability did not affect CM or BNST activation. These results suggest a BNST role in anxious anticipation and highlight the need for further research clarifying the temporal response characteristics of these regions.

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High-resolution and cell-type-specific photostimulation mapping shows weak excitatory vs. strong inhibitory inputs in the bed nucleus of the stria terminalis

Journal of Neurophysiology ◽

10.1152/jn.01148.2015 ◽

2016 ◽

Vol 115 (6) ◽

pp. 3204-3216 ◽

Cited By ~ 5

Author(s):

Xiangmin Xu ◽

Taruna Ikrar ◽

Yanjun Sun ◽

Rommel Santos ◽

Todd C. Holmes ◽

...

Keyword(s):

High Resolution ◽

Functional Organization ◽

Stria Terminalis ◽

Cell Type ◽

Experimental Conditions ◽

Bed Nucleus ◽

Local Circuit ◽

Synaptic Inputs ◽

Cell Type Specific ◽

Local Circuits

The bed nucleus of the stria terminalis (BNST) is a key component of the extended amygdala and has been implicated in anxiety and addiction. As individual neurons function within neural circuits, it is important to understand local microcircuits and larger network connections of identified neuronal types and understand how maladaptive changes in the BNST neural networks are induced by stress and drug abuse. However, due to limitations of classic anatomical and physiological methods, the local circuit organization of synaptic inputs to specific BNST neuron types is not well understood. In this study, we report on the application of high-resolution and cell-type-specific photostimulation methodology developed in our laboratory to local circuit mapping in the BNST. Under calibrated experimental conditions, laser photostimulation via glutamate uncaging or channelrhodopsin-2 photoactivation evokes spiking of BNST neurons perisomatically, without activating spikes from axons of passage or distal dendrites. Whole cell recordings, combined with spatially restricted photostimulation of presynaptic neurons at many different locations over a large region, allow high-resolution mapping of presynaptic input sources to single recorded neurons in the BNST. We constructed maps of synaptic inputs impinging onto corticotrophin-releasing hormone-expressing (CRH+) BNST neurons in the dorsolateral BNST and found that the CRH+ neurons receive predominant local inhibitory synaptic connections with very weak excitatory connections. Through cell-type-specific optogenetic stimulation mapping, we generated maps of somatostatin-expressing neuron-specific inhibitory inputs to BNST neurons. Taken together, the photostimulation-based techniques offer us powerful tools for determining the functional organization of local circuits of specific BNST neuron types.

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