Differential Responses of Thalamic Reticular Neurons to Nociception in Freely Behaving Mice

Huh, Yeowool,Cho, Jeiwon Frontiers Media S.A. 2016 Frontiers in Behavioral Neuroscience Vol.10 No.-

<P>Pain serves an important protective role. However, it can also have debilitating adverse effects if dysfunctional, such as in pathological pain conditions. As part of the thalamocortical circuit, the thalamic reticular nucleus (TRN) has been implicated to have important roles in controlling nociceptive signal transmission. However studies on how TRN neurons, especially how TRN neuronal subtypes categorized by temporal bursting firing patterns—typical bursting, atypical bursting and non-bursting TRN neurons—contribute to nociceptive signal modulation is not known. To reveal the relationship between TRN neuronal subtypes and modulation of nociception, we simultaneously recorded behavioral responses and TRN neuronal activity to formalin induced nociception in freely moving mice. We found that typical bursting TRN neurons had the most robust response to nociception; changes in tonic firing rate of typical TRN neurons exactly matched changes in behavioral nociceptive responses, and burst firing rate of these neurons increased significantly when behavioral nociceptive responses were reduced. This implies that typical TRN neurons could critically modulate ascending nociceptive signals. The role of other TRN neuronal subtypes was less clear; atypical bursting TRN neurons decreased tonic firing rate after the second peak of behavioral nociception and the firing rate of non-bursting TRN neurons mostly remained at baseline level. Overall, our results suggest that different TRN neuronal subtypes contribute differentially to processing formalin induced sustained nociception in freely moving mice.</P>

Urethane anesthesia depresses activities of thalamocortical neurons and alters its response to nociception in terms of dual firing modes

Huh, Yeowool,Cho, Jeiwon Frontiers Media S.A. 2013 Frontiers in Behavioral Neuroscience Vol.7 No.-

<P>Anesthetics are often used to characterize the activity of single neurons <I>in vivo</I> for their advantages such as reduction of noise level and convenience in noxious stimulations. Urethane has been a widely used anesthetic in thalamic studies under the assumption that sensory signals are still relayed to the thalamus under urethane anesthesia and that thalamic response would therefore reflect the response of the awake state. We tested this assumption by comparing thalamic activity in terms of tonic and burst firing modes during “the awake state” or under “urethane anesthesia” using the extracellular single unit recording technique. We first tested how thalamic relay neurons respond to the introduction of urethane, and then tested how urethane influences thalamic discharges under formalin-induced nociception. Urethane significantly depressed overall firing rates of thalamic relay neurons, which was sustained despite the delayed increase of burst activity over a 4 h recording period. Thalamic response to nociception under anesthesia was also similar overall except for the slight and transient increase of burst activity. Overall, results demonstrated that urethane suppresses the activity of thalamic relay neurons and that, despite the slight fluctuation of burst firing, formalin-induced nociception cannot significantly change the firing pattern of thalamic relay neurons that was caused by urethane.</P>

Brain stimulation patterns emulating endogenous thalamocortical input to parvalbumin-expressing interneurons reduce nociception in mice

Huh, Yeowool,Jung, Dahee,Seo, Taeyoon,Sun, Sukkyu,Kim, Su Hyun,Rhim, Hyewhon,Chung, Sooyoung,Kim, Chong-Hyun,Kwon, Youngwoo,Bikson, Marom,Chung, Yong-an,Kim, Jeansok J.,Cho, Jeiwon Elsevier 2018 Brain stimulation Vol.11 No.5

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>The bursting pattern of thalamocortical (TC) pathway dampens nociception. Whether brain stimulation mimicking endogenous patterns can engage similar sensory gating processes in the cortex and reduce nociceptive behaviors remains uninvestigated.</P> <P><B>Objective</B></P> <P>We investigated the role of cortical parvalbumin expressing (PV) interneurons within the TC circuit in gating nociception and their selective response to TC burst patterns. We then tested if transcranial magnetic stimulation (TMS) patterned on endogenous nociceptive TC bursting modulate nociceptive behaviors.</P> <P><B>Methods</B></P> <P>The switching of TC neurons between tonic (single spike) and burst (high frequency spikes) firing modes may be a critical component in modulating nociceptive signals. Deep brain electrical stimulation of TC neurons and immunohistochemistry were used to examine the differential influence of each firing mode on cortical PV interneuron activity. Optogenetic stimulation of cortical PV interneurons assessed a direct role in nociceptive modulation. A new TMS protocol mimicking thalamic burst firing patterns, contrasted with conventional continuous and intermittent theta burst protocols, tested if TMS patterned on endogenous TC activity reduces nociceptive behaviors in mice.</P> <P><B>Results</B></P> <P>Immunohistochemical evidence confirmed that burst, but not tonic, deep brain stimulation of TC neurons increased the activity of PV interneurons in the cortex. Both optogenetic activation of PV interneurons and TMS protocol mimicking thalamic burst reduced nociceptive behaviors.</P> <P><B>Conclusions</B></P> <P>Our findings suggest that burst firing of TC neurons recruits PV interneurons in the cortex to reduce nociceptive behaviors and that neuromodulation mimicking thalamic burst firing may be useful for modulating nociception.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Electrical stimulation mimicking thalamic bursts activate cortical PV interneurons. </LI> <LI> Selective optical activation of PV interneurons reduces nociceptive behaviors. </LI> <LI> TMS mimicking ‘Thalamic burst’ reduces nociceptive behaviors in mice. </LI> </UL> </P>

The Ventral Midline Thalamus Mediates Hippocampal Spatial Information Processes upon Spatial Cue Changes

Jung, Dahee,Huh, Yeowool,Cho, Jeiwon Society for Neuroscience 2019 The Journal of neuroscience Vol.39 No.12

<P>The ventral midline thalamus, consisting of the reuniens and rhomboid nuclei (RE/Rh), is a thalamic structure interconnected with the limbic systems including the hippocampus. Recently, many studies have revealed that this structure plays distinctive roles in spatial learning and memory in collaboration with hippocampal functions. However, what aspects of spatial information process are influenced by the RE/Rh is not clearly known. To elucidate the roles of RE/Rh in spatial information processing and its effects on hippocampal activity, specifically with the manipulation of spatial contents, we measured hippocampal-dependent spatial memory performance and hippocampal place cell activities after RE/Rh lesion using male C57BL/6J × 129/SvJae hybrid mice. We found that the lesion altered the behavioral aptitude in recognizing locational changes of an object. Furthermore, CA1 place cells in the lesion group showed different spatial representation patterns in recognizing the environment with cue locational changes compared with the control group. Interestingly, the patterns of CA1 place cells in recognizing the same environment previously visited were not disrupted in the lesion group compared with the control group. These findings demonstrate that the ventral midline thalamus (RE/Rh) is important in recognizing the spatial relationships, especially when spatial rearrangement of cue position was introduced.</P><P><B>SIGNIFICANCE STATEMENT</B> The ventral midline thalamic nuclei (reuniens and rhomboid) interact with the hippocampus to influence various cognitive functions requiring spatial memories, yet what aspects of spatial information process are influenced by these nuclei is not clearly known. Here, we reveal that these nuclei play a crucial role in modulating hippocampal properties only with locational rearrangement of cues, not with the familiar arrangement. These nuclei are distinctively involved in cue-dependent spatial information processes of CA1 place cells. In particular, we suggest that these nuclei modulate spatial information processing on discrete components, especially when the spatial cue relationship is modified.</P>

Dual-purpose probe applicable to permittivity measurements and ablation of biological materials

Seo, Taeyoon,Oh, Seongwoog,Huh, Yeowool,Cho, Jeiwon,Kwon, Youngwoo Institution of Electrical Engineers 2018 Electronics letters Vol.54 No.3

Noninvasive Brain Stimulation Using a Modulated Microwave Signal

Taeyoon Seo,Seongwoog Oh,Dahee Jung,Yeowool Huh,Jeiwon Cho,Youngwoo Kwon 한국전자파학회JEES 2018 Journal of Electromagnetic Engineering and Science Vol.18 No.1

We propose a microwave signal generation system for brain stimulation. The existing brain stimulation system uses a signal of several tens of kHz, and the magnetic field distribution is wide. Microwave is used to locally limit the distribution of the electromagnetic field and to change the action potential of the cell with less power. The switch modulates the microwave signal to obtain a pulse envelope. The action potential of the cell can be controlled to the excitation/inhibition state by adjusting the repetition frequency. These results are confirmed by measuring the cell potential of the mouse brain.