scholarly journals Modulation of fear generalization by the zona incerta

2018 ◽  
Author(s):  
Archana Venkataraman ◽  
Natalia Brody ◽  
Preethi Reddi ◽  
Jidong Guo ◽  
Donald Rainnie ◽  
...  
Keyword(s):  
Inverse Relationship ◽  
Sensorimotor Integration ◽  
Sensory Information ◽  
Brain Regions ◽  
Zona Incerta ◽  
Sensory Discrimination ◽  
Defensive Responses ◽  
Fear Generalization ◽  
Stimulation Of ◽  
Do So

Fear expressed towards threat-associated stimuli is an adaptive behavioral response. In contrast, the generalization of fear responses toward non-threatening cues is maladaptive and a debilitating dimension of trauma- and anxiety-related disorders. Expressing fear to appropriate stimuli and suppressing fear generalization requires integration of relevant sensory information and motor output. While thalamic and sub-thalamic brain regions play important roles in sensorimotor integration, very little is known about the contribution of these regions to the phenomenon of fear generalization. In this study, we sought to determine whether fear generalization could be modulated by the zona incerta (ZI), a sub-thalamic brain region that influences sensory discrimination, defensive responses, and retrieval of fear memories. To do so, we combined differential intensity-based auditory fear conditioning protocols in mice with C-FOS immunohistochemistry and DREADD-based manipulation of neuronal activity in the ZI. C-FOS immunohistochemistry revealed an inverse relationship between ZI activation and fear generalization with the ZI being less active in animals that generalized fear. In agreement with this relationship, chemogenetic inhibition of the ZI resulted in fear generalization, while chemogenetic activation of the ZI suppressed fear generalization. Furthermore, targeted stimulation of GABAergic cells in the ZI reduced fear generalization. To conclude, our data suggest that stimulation of the ZI could be used to treat fear generalization in the context of trauma- and anxiety-related disorders.

scholarly journals Modulation of fear generalization by the zona incerta

2019 ◽  
Vol 116 (18) ◽  
pp. 9072-9077 ◽  
Author(s):  
Archana Venkataraman ◽  
Natalia Brody ◽  
Preethi Reddi ◽  
Jidong Guo ◽  
Donald Gordon Rainnie ◽  
...  
Keyword(s):  
Sensorimotor Integration ◽  
Sensory Information ◽  
Brain Regions ◽  
Designer Drugs ◽  
Zona Incerta ◽  
Sensory Discrimination ◽  
Defensive Responses ◽  
Fear Generalization ◽  
Stimulation Of ◽  
Do So

Fear expressed toward threat-associated stimuli is an adaptive behavioral response. In contrast, the generalization of fear responses toward nonthreatening cues is a maladaptive and debilitating dimension of trauma- and anxiety-related disorders. Expressing fear to appropriate stimuli and suppressing fear generalization require integration of relevant sensory information and motor output. While thalamic and subthalamic brain regions play important roles in sensorimotor integration, very little is known about the contribution of these regions to the phenomenon of fear generalization. In this study, we sought to determine whether fear generalization could be modulated by the zona incerta (ZI), a subthalamic brain region that influences sensory discrimination, defensive responses, and retrieval of fear memories. To do so, we combined differential intensity-based auditory fear conditioning protocols in mice with C-FOS immunohistochemistry and designer receptors exclusively activated by designer drugs (DREADDs)-based manipulation of neuronal activity in the ZI. C-FOS immunohistochemistry revealed an inverse relationship between ZI activation and fear generalization: The ZI was less active in animals that generalized fear. In agreement with this relationship, chemogenetic inhibition of the ZI resulted in fear generalization, while chemogenetic activation of the ZI suppressed fear generalization. Furthermore, targeted stimulation of GABAergic cells in the ZI reduced fear generalization. To conclude, our data suggest that stimulation of the ZI could be used to treat fear generalization in the context of trauma- and anxiety-related disorders.

scholarly journals Incerto-thalamic modulation of fear via GABA and dopamine

2021 ◽  
Author(s):  
Archana Venkataraman ◽  
Sarah C. Hunter ◽  
Maria Dhinojwala ◽  
Diana Ghebrezadik ◽  
JiDong Guo ◽  
...  
Keyword(s):  
Brain Regions ◽  
Zona Incerta ◽  
Dependent Manner ◽  
Post Traumatic Stress ◽  
Functional Roles ◽  
Functional Connections ◽  
Optogenetic Stimulation ◽  
Fear Generalization ◽  
Stimulation Of

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

scholarly journals Dystonic tics induced by deep brain stimulation of the posterior subthalamic area for essential tremor

2017 ◽  
Vol 126 (2) ◽  
pp. 386-390 ◽  
Author(s):  
Arjun S. Chandran ◽  
Stuti Joshi ◽  
Megan Thorburn ◽  
Rick Stell ◽  
Christopher R. P. Lind
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Case Series ◽  
Brain Regions ◽  
Tic Disorders ◽  
Zona Incerta ◽  
Brain Target ◽  
Deep Brain ◽  
Stimulation Of

OBJECTIVE The posterior subthalamic area (PSA) is a promising target of deep brain stimulation (DBS) for medication-refractory essential tremor (ET). This case series describes a novel adverse effect manifesting as dystonic tics in patients with ET undergoing DBS of the PSA. METHODS Six patients with ET received electrode implants for DBS of the dorsal and caudal zona incerta subregions of the PSA. RESULTS Five of the 6 patients developed dystonic tics soon after clinical programming. These tics were of varying severity and required reduction of the electrical stimulation amplitude. This reduction resolved tic occurrence without significantly affecting ET control. Dystonic tics were not observed in 39 additional patients who underwent DBS of the same brain regions for controlling non-ET movement disorders. CONCLUSIONS The pathophysiology of tic disorders is poorly understood and may involve the basal ganglia and related cortico-striato-thalamo-cortical circuits. This series is the first report of DBS-induced tics after stimulation of any brain target. Although the PSA has not previously been implicated in tic pathophysiology, it may be a candidate region for future studies.

The zona incerta modulates spontaneous spike-wave discharges in the rat

2013 ◽  
Vol 109 (10) ◽  
pp. 2505-2516 ◽  
Author(s):  
Fu-Zen Shaw ◽  
Yi-Fang Liao ◽  
Ruei-Feng Chen ◽  
Yu-Hsing Huang ◽  
Rick C. S. Lin
Keyword(s):  
Functional Role ◽  
Significant Inhibition ◽  
Zona Incerta ◽  
Obvious Effect ◽  
Spike Wave Discharges ◽  
Long Evans ◽  
Oscillation Frequencies ◽  
Spike Wave ◽  
Stimulation Of

The contribution of the zona incerta (ZI) of the thalamus on spike-wave discharges (SWDs) was investigated. Chronic recordings of bilateral cortices, bilateral vibrissa muscle, and unilateral ZI were performed in Long-Evans rats to examine the functional role of SWDs. Rhythmic ZI activity appeared at the beginning of SWD and was accompanied by higher-oscillation frequencies and larger spike magnitudes. Bilateral lidocaine injections into the mystacial pads led to a decreased oscillation frequency of SWDs, but the phenomenon of ZI-related spike magnitude enhancement was preserved. Moreover, 800-Hz ZI microstimulation terminates most of the SWDs and whisker twitching (WT; >80%). In contrast, 200-Hz ZI microstimulation selectively stops WTs but not SWDs. Stimulation of the thalamic ventroposteriomedial nucleus showed no obvious effect on terminating SWDs. A unilateral ZI lesion resulted in a significant reduction of 7- to 12-Hz power of both the ipsilateral cortical and contralateral vibrissae muscle activities during SWDs. Intraincertal microinfusion of muscimol showed a significant inhibition on SWDs. Our present data suggest that the ZI actively modulates the SWD magnitude and WT behavior.

Compressed sensorimotor-to-transmodal hierarchical organization in schizophrenia

2021 ◽  
pp. 1-14
Author(s):  
Debo Dong ◽  
Dezhong Yao ◽  
Yulin Wang ◽  
Seok-Jun Hong ◽  
Sarah Genon ◽  
...  
Keyword(s):  
Sensory Information ◽  
Resting State Fmri ◽  
Brain Regions ◽  
High Order ◽  
Hierarchical Organization ◽  
System Level ◽  
Integrative System ◽  
Sensorimotor Region ◽  
Cortical Hierarchy ◽  
High Level

Abstract Background Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Methods We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). Results We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal−parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). Conclusions The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory−motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.

Synaptic Responses of Neurons Controlling the Parotid and von Ebner Salivary Glands in Rats to Stimulation of the Solitary Nucleus and Tract

2008 ◽  
Vol 99 (3) ◽  
pp. 1267-1273 ◽  
Author(s):  
Takeshi Suwabe ◽  
Hideyuki Fukami ◽  
Robert M. Bradley
Keyword(s):  
Salivary Glands ◽  
Sensory Information ◽  
Salivary Secretion ◽  
Afferent Input ◽  
Membrane Hyperpolarization ◽  
Neuron Response ◽  
Glutamate Receptor Antagonists ◽  
Autonomic Neurons ◽  
Reflex Stimulation ◽  
Stimulation Of

Salivary secretion results from reflex stimulation of autonomic neurons via afferent sensory information relayed to neurons in the rostral nucleus of the solitary tract (rNST), which synapse with autonomic neurons of the salivatory nuclei. We investigated the synaptic properties of the afferent sensory connection to neurons in the inferior salivatory nucleus (ISN) controlling the parotid and von Ebner salivary glands. Mean synaptic latency recorded from parotid gland neurons was significantly shorter than von Ebner gland neurons. Superfusion of GABA and glycine resulted in a concentration-dependent membrane hyperpolarization. Use of glutamate receptor antagonists indicated that both AMPA and N-methyl-d-aspartate (NMDA) receptors are involved in the evoked excitatory postsynaptic potentials (EPSPs). Inhibitory postsynaptic potential (IPSP) amplitude increased with higher intensity ST stimulation. Addition of the glycine antagonist strychnine did not affect the amplitude of the IPSPs significantly. The GABAA receptor antagonist, bicuculline (BMI) or mixture of strychnine and BMI abolished the IPSPs in all neurons. IPSP latency was longer than EPSP latency, suggesting that more than one synapse is involved in the inhibitory pathway. Results show that ISN neurons receive both excitatory and inhibitory afferent input mediated by glutamate and GABA respectively. The ISN neuron response to glycine probably derives from descending connections. Difference in the synaptic characteristics of ISN neurons controlling the parotid and von Ebner glands may relate to the different function of these two glands.

scholarly journals Detour learning ability and the effect of novel sensory cues on learning in Australian bull ants, Myrmecia midas

2021 ◽  
Author(s):  
Muzahid Islam ◽  
Sudhakar Deeti ◽  
Zakia Mahmudah ◽  
J. Frances Kamhi ◽  
Ken Cheng
Keyword(s):  
Animal Cognition ◽  
Sensory Information ◽  
Learning Ability ◽  
Visual Environment ◽  
Sensory Cues ◽  
Complex Environment ◽  
Physical Barriers ◽  
Tactile Cues ◽  
Detour Learning ◽  
Do So

ABSTRACTMany animals navigate in a structurally complex environment which requires them to detour around physical barriers that they encounter. While many studies in animal cognition suggest that they are able to adeptly avoid obstacles, it is unclear whether a new route is learned to navigate around these barriers and, if so, what sensory information may be used to do so. We investigated detour learning ability in the Australian bull ant, Myrmecia midas, which primarily uses visual landmarks to navigate. We first placed a barrier on the ants’ natural path of their foraging tree. Initially, 46% of foragers were unsuccessful in detouring the obstacle. In subsequent trips, the ants became more successful and established a new route. We observed up to eight successful foraging trips detouring around the barrier. When we subsequently changed the position of the barrier, made a new gap in the middle of the obstacle, or removed the barrier altogether, ants mostly maintained their learned motor routine, detouring with a similar path as before, suggesting that foragers were not relying on barrier cues and therefore learned a new route around the obstacle. In additional trials, when foragers encountered new olfactory or tactile cues, or the visual environment was blocked, their navigation was profoundly disrupted. These results suggest that changing sensory information, even in modalities that foragers do not usually need for navigation, drastically affects the foragers’ ability to successful navigate.Subject CategoryNeuroscience and Cognition

scholarly journals Speech Function Following Deep Brain Stimulation of the Caudal Zona Incerta: Effects of Habitual and High-Amplitude Stimulation

2021 ◽  
pp. 1-13
Author(s):  
Linda Sandström ◽  
Ellika Schalling ◽  
Fredrik Karlsson ◽  
Patric Blomstedt ◽  
Lena Hartelius
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Amplitude ◽  
Nonparametric Tests ◽  
Zona Incerta ◽  
Maximal Amplitude ◽  
Significant Group ◽  
Preliminary Study ◽  
Deep Brain ◽  
Stimulation Of

Purpose Deep brain stimulation (DBS) is often successful in alleviating motor symptoms of essential tremor (ET); however, DBS may also induce adverse speech effects. The caudal zona incerta (cZi) is a promising DBS target for tremor, but less is known about the consequences of cZi DBS for speech. This preliminary study examined how habitual cZi DBS and cZi stimulation at high amplitudes may affect speech function in persons with ET. Method Fourteen participants with ET were evaluated: off stimulation, on habitual cZi DBS, and with unilateral cZi stimulation at increasing stimulation amplitudes. At each stimulation condition, the participants read three 16-word sentences. Two speech-language pathologists made audio-perceptual consensus ratings of overall speech function, articulation, and voice using a visual sort and rate method. Rated functions when off stimulation, on habitual cZi DBS, and at maximal-amplitude stimulation were compared using Friedman nonparametric tests. For participants with bilateral habitual DBS ( n = 5), the effects of bilateral and unilateral stimulation were described in qualitative terms. Results Habitual cZi DBS had no significant group-level effect on any of the investigated speech parameters. Maximal-amplitude stimulation had a small but significant negative effect on articulation. Participants with reduced articulatory precision ( n = 9) had more medially placed electrodes than the nonaffected group ( n = 5). Bilateral and unilateral left stimulation had comparable effects on speech. Conclusions Findings from this preliminary study of cZi DBS indicate that speech is generally not affected by stimulation at habitual levels. High-amplitude cZi stimulation may, however, induce adverse effects, particularly on articulation. Instances of decreased articulatory function were associated with stimulation of more medial electrode contacts, which could suggest cerebello-rubrospinal involvement.

scholarly journals The Connectivity Index: An Effective Metric for Grading Epileptogenicity

2019 ◽  
Author(s):  
Qi Yan ◽  
Nicolas Gaspard ◽  
Hitten P Zaveri ◽  
Hal Blumenfeld ◽  
Lawrence J. Hirsch ◽  
...  
Keyword(s):  
Average Distance ◽  
Single Pulse ◽  
Brain Regions ◽  
Control Site ◽  
Connectivity Index ◽  
Evoked Responses ◽  
Seizure Onset ◽  
Seizure Onset Zone ◽  
Site Of Stimulation ◽  
Stimulation Of

AbstractObjectiveTo investigate the performance of a metric of functional connectivity to classify and grade the excitability of brain regions based on evoked potentials to single pulse electrical stimulation (SPES).MethodsPatients who received 1-Hz frequency stimulation between 2003 and 2014 at Yale at prospectively selected contacts were included. The stimulated contacts were classified as seizure onset zone (SOZ), highly irritative zone (IZp) or control. Response contacts were classified as seizure onset zone (SOZ), active interictal (IZp), quiet or other. The normalized number of responses was defined as the number of contacts with any evoked responses divided by the total number of recorded contacts, and the normalized distance is the ratio of the average distance between the site of stimulation and sites of evoked responses to the average distances between the site of stimulation and all other recording contacts. A new metric we labeled the connectivity index (CI) is defined as the product of the two values.Results57 stimulation-sessions in 22-patients were analyzed. The connectivity index (CI) of the SOZ was higher than control (median CI of 0.74 vs. 0.16, p = 0.0002). The evoked responses after stimulation of SOZ were seen at further distance compared to control (median normalized distance 0.96 vs. 0.62, p = 0.0005). It was 1.8 times more likely to record a response at SOZ than in non-epileptic contacts after stimulation of a control site. Habitual seizures were triggered in 27% of patients and 35 % of SOZ contacts (median stimulation intensity 4 mA) but in none of the control or IZp contacts. Non-SOZ contacts in multifocal or poor surgical outcome cases had a higher CI than non-SOZ contacts in those with localizable onsets (medians CI of 0.5 vs. 0.12, p = 0.04). There was a correlation between the stimulation current intensity and the normalized number of evoked responses (r = + 0.49, p 0.01) but not with distance (r = + 0.1, p 0.64)ConclusionsWe found enhanced connectivity when stimulating the SOZ compared to stimulating control contacts; responses were more distant as well. Habitual auras and seizures provoked by SPES were highly predictive of brain sites involved in seizure generation.

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