Zona incerta (ZI) is a functionally mysterious subthalamic nucleus containing mostly inhibitory neurons. Here, we discover that GABAergic neurons in the rostral sector of ZI (ZIr) directly innervate excitatory but not inhibitory neurons in the dorsolateral and ventrolateral compartments of periaqueductal gray (PAG), which can drive flight and freezing behaviors respectively. Optogenetic activation of ZIr neurons or their projections to PAG reduces both sound-induced innate flight response and conditioned freezing response, while optogenetic suppression of these neurons enhances these defensive behaviors, likely through a mechanism of gain modulation. ZIr activity progressively increases during extinction of conditioned freezing response, and suppressing ZIr activity impairs the expression of fear extinction. Furthermore, ZIr is innervated by the medial prefrontal cortex (mPFC), and silencing mPFC prevents the increase of ZIr activity during extinction and the expression of fear extinction. Together, our results suggest that ZIr is engaged in modulating defense behaviors.

In humans and non-human primates (NHP), white matter neurons (WMNs) persist beyond early development. Their functional importance is largely unknown, but they have both corticothalamic and corticocortical connectivity and at least one subpopulation has been implicated in vascular regulation and sleep. Several other studies have reported that the density of WMNs in humans is altered in neuropathological or psychiatric conditions. The present investigation evaluates and compares the density of superficial and deep WMNs in frontal (FR), temporal (TE), and parietal (Par) association regions of four young adult and four aged male rhesus monkeys. A major aim was to determine whether there was age-related neuronal loss, as might be expected given the substantial age-related changes known to occur in the surrounding white matter environment. Neurons were visualized by immunocytochemistry for Neu-N in coronal tissue sections (30 μm thickness), and neuronal density was assessed by systematic random sampling. Per 0.16 mm2 sampling box, this yielded about 40 neurons in the superficial WM and 10 in the deep WM. Consistent with multiple studies of cell density in the cortical gray matter of normal brains, neither the superficial nor deep WM populations showed statistically significant age-related neuronal loss, although we observed a moderate decrease with age for the deep WMNs in the frontal region. Morphometric analyses, in contrast, showed significant age effects in soma size and circularity. In specific, superficial WMNs were larger in FR and Par WM regions of the young monkeys; but in the TE, these were larger in the older monkeys. An age effect was also observed for soma circularity: superficial WMNs were more circular in FR and Par of the older monkeys. This second, morphometric result raises the question of whether other age-related morphological, connectivity, or molecular changes occur in the WMNs. These could have multiple impacts, given the wide range of putative WMN functions and their involvement in both corticothalamic and corticocortical circuitry.

Zona incerta (ZI) is a largely inhibitory subthalamic region connecting with many brain areas. Early studies have suggested involvement of ZI in various functions such as visceral activities, arousal, attention and locomotion, but the specific roles of different ZI subdomains or cell-types have not been well examined. Recent studies combining optogenetics, behavioral assays, neural tracing and neural activity recording reveal novel functional roles of ZI depending on specific input-output connectivity patterns. Here, we review these studies and summarize functions of ZI into four categories: sensory integration, behavioral output control, motivational drive and neural plasticity. In view of these new findings, we propose that ZI serves as an integrative node for global modulation of behaviors and physiological states.

Animals exhibit innate defense behaviors in response to approaching threats cued by the dynamics of sensory inputs of various modalities. The underlying neural circuits have been mostly studied in the visual system, but remain unclear for other modalities. Here, by utilizing sounds with increasing (vs. decreasing) loudness to mimic looming (vs. receding) objects, we find that looming sounds elicit stereotypical sequential defensive reactions: freezing followed by flight. Both behaviors require the activity of auditory cortex, in particular the sustained type of responses, but are differentially mediated by corticostriatal projections primarily innervating D2 neurons in the tail of the striatum and corticocollicular projections to the superior colliculus, respectively. The behavioral transition from freezing to flight can be attributed to the differential temporal dynamics of the striatal and collicular neurons in their responses to looming sound stimuli. Our results reveal an essential role of the striatum in the innate defense control.

The sense of touch is represented by neural activity patterns evoked by mechanosensory input forces. The rodent whisker system is exceptional for studying the neurophysiology of touch in part because these forces can be precisely computed from video of whisker deformation. We evaluate the accuracy of a standard model of whisker bending, which assumes quasi-static dynamics and a linearly tapered conical profile, using controlled whisker deflections. We find significant discrepancies between model and experiment: real whiskers bend more than predicted upon contact at locations in the middle of the whisker and less at distal locations. Thus whiskers behave as if their stiffness near the base and near the tip is larger than expected for a homogeneous cone. We assess whether contact direction, friction, inhomogeneous elasticity, whisker orientation, or nonconical shape could explain these deviations. We show that a thin-middle taper of mouse whisker shape accounts for the majority of this behavior. This taper is conserved across rows and columns of the whisker array. The taper has a large effect on the touch-evoked forces and the ease with which whiskers slip past objects, which are key drivers of neural activity in tactile object localization and identification. This holds for orientations with intrinsic whisker curvature pointed toward, away from, or down from objects, validating two-dimensional models of simple whisker-object interactions. The precision of computational models relating sensory input forces to neural activity patterns can be quantitatively enhanced by taking thin-middle taper into account with a simple corrective function that we provide.