scholarly journals Enhancing GABAergic Tone in the Rostral Nucleus of the Solitary Tract Reconfigures Sensorimotor Neural Activity

2020 ◽  
Author(s):  
Joshua D. Sammons ◽  
Caroline E. Bass ◽  
Jonathan D. Victor ◽  
Patricia M. Di Lorenzo

ABSTRACTRecent work has shown that most cells in the rostral, gustatory portion of the nucleus tractus solitarius (rNTS) in awake, freely licking rats show lick-related firing. However, the relationship between taste-related and lick-related activity in rNTS remains unclear. Here, we tested if GABA-derived inhibitory activity regulates the balance of lick- and taste-driven neuronal activity. Combinatorial viral tools were used to restrict expression of ChR2-EYFP to GAD1+ GABAergic neurons. Viral infusions were bilateral in rNTS. 2-4wks later, an optical fiber attached to 8-16 drivable microwires was implanted into the rNTS. After recovery, water-deprived rats were presented with taste stimuli in an experimental chamber. Trials were 5 consecutive taste licks [NaCl, KCl, NH4Cl, sucrose, MSG/IMP, citric acid, quinine, or artificial saliva (AS)] separated by 5 AS licks on a VR5 schedule. Each taste lick triggered a 1s train of laser light (25Hz; 473nm; 8-10mW) in a random half of the trials. In all, 113 cells were recorded in the rNTS, 50 responded to one or more taste stimuli without GABA enhancement. Selective changes in response magnitude (spike count) within cells shifted across unit patterns but preserved inter-stimulus relationships. Cells where enhanced GABAergic tone increased lick coherence conveyed more information distinguishing basic taste qualities and different salts than other cells. In addition, GABA activation significantly amplified the amount of information that discriminated palatable vs. unpalatable tastants. By dynamically regulating lick coherence and remodeling the across-unit response patterns to taste, enhancing GABAergic tone in rNTS reconfigures the neural activity reflecting sensation and movement.Significance StatementThe rostral nucleus tractus solitarius (rNTS) is the first structure in the central gustatory pathway. Electrophysiological recordings from the rNTS in awake, freely-licking animals show that cells in this area have lick- as well as taste-related activity, but the relationship between these characteristics is not well understood. Here, we showed evidence that GABA activation can dynamically regulate both of these two properties in rNTS cells to enhance the information conveyed, especially about palatable vs. unpalatable tastants. These data provide insights into the role of inhibitory activity in the rNTS.

2019 ◽  
Author(s):  
Michael S Weiss ◽  
Andras Hajnal ◽  
Krzysztof Czaja ◽  
Patricia M Di Lorenzo

Taste perception changes with obesity but the underlying neural changes remain poorly understood. To address this issue, we recorded taste responses from single cells in the nucleus tractus solitarius (NTS, the fist central synapse in the gustatory circuit) in awake, diet-induced obese [(DIO; ≥8wks on a high-energy diet (HED)] and lean rats. Rats were implanted with a bundle of microelectrodes in the NTS and allowed to recover. Water-deprived rats were allowed to freely lick various tastants in an experimental chamber. Taste stimuli included an array of sapid stimuli dissolved in artificial saliva (AS). Each taste trial consisted of 5 consecutive licks followed by 5 AS licks presented on a VR5 schedule. Results showed that taste responses in NTS cells in DIO rats (n=49) were smaller in magnitude, shorter in duration and longer in latency that those in lean rats (n=74). However, there were proportionately more taste-responsive cells in DIO than in lean rats. Lick coherence in DIO rats was significantly lower than in lean rats, both in taste-responsive and lick-related cells (n=172 in lean; n=65 in DIO). Analyses of temporal coding showed that taste cells in DIO rats conveyed less information about taste quality than cells in lean rats. Collectively, results suggest that a HED produces blunted, but more prevalent, responses to taste in the NTS and a weakened association of taste responses with ingestive behavior. These neural adaptations may represent both negative effects and compensatory mechanisms of a HED that may underlie deficits in taste-related behavior associated with obesity.


2019 ◽  
Author(s):  
Manuel Gomez-Ramirez ◽  
Alexander I. More ◽  
Nina G. Friedman ◽  
Ute Hochgeschwender ◽  
Christopher I. Moore

ABSTRACTBioLuminescent (BL) light production can modulate neural activity and behavior through coexpressed OptoGenetic (OG) elements, an approach termed ‘BL-OG’. Yet, the relationship between BL-OG effects and bioluminescent photon emission has not been characterized in vivo. Further, the degree to which BL-OG effects strictly depend on optogenetic mechanisms driven by bioluminescent photons is unknown. Crucial to every neuromodulation method is whether the activator shows a dynamic concentration range driving robust, selective, and non-toxic effects. We systematically tested the effects of four key components of the BL-OG mechanism (luciferin, oxidized luciferin, luciferin vehicle, and bioluminescence), and compared these against effects induced by the Luminopsin-3 (LMO3) BL-OG molecule, a fusion of slow burn Gaussia luciferase (sbGLuc) and Volvox ChannelRhodopsin-1 (VChR1). We performed combined bioluminescence imaging and electrophysiological recordings while injecting specific doses of Coelenterazine (substrate for sbGluc), Coelenteramide (CTM, the oxidized product of CTZ), or CTZ vehicle. CTZ robustly drove activity in mice expressing LMO3, with photon production proportional to firing rate. In contrast, low and moderate doses of CTZ, CTM, or vehicle did not modulate activity in mice that did not express LMO3. We also failed to find bioluminescence effects on neural activity in mice expressing an optogenetically non-sensitive LMO3 variant. We observed weak responses to the highest dose of CTZ in control mice, but these effects were significantly smaller than those observed in the LMO3 group. These results show that in neocortex in vivo, there is a large CTZ range wherein BL-OG effects are specific to its active chemogenetic mechanism.


2019 ◽  
Author(s):  
R. Frömer ◽  
A. Shenhav

AbstractPrevious research suggests that people evaluate options in at least two ways: (1) appraising their overall value and (2) choosing between them. Here we test whether these processes are temporally dissociable, with appraisal-related processes tied to the time one’s options appear and choice-related processes tied to the time a decision is made. We recorded EEG while participants individually rated and subsequently made choices between consumer goods. As predicted, we found appraisal-related neural activity locked to the onset of the stimuli and choice-related activity locked to (and preceding) the response. Patterns of appraisal- and choice-related activity were further associated with distinct topographical profiles. Using a novel neural index of one’s certainty about a given item’s value, we also provide evidence that choices and choice-related activity were further modulated by this option-specific value certainty. Taken together, our results support the hypothesis that spatiotemporally distinct mechanisms underlie appraisal and choice, suggesting that commonly observed neural correlates of choice value may reflect either or both of these processes.


2019 ◽  
Vol 121 (2) ◽  
pp. 634-645 ◽  
Author(s):  
Alexander J. Denman ◽  
Joshua D. Sammons ◽  
Jonathan D. Victor ◽  
Patricia M. Di Lorenzo

Theories of neural coding in the taste system typically rely exclusively on data gleaned from taste-responsive cells. However, even in the nucleus tractus solitarius (NTS), the first stage of central processing, neurons with taste selectivity coexist with neurons whose activity is linked to motor behavior related to ingestion. We recorded from a large ( n = 324) sample of NTS neurons recorded in awake rats, examining both their taste selectivity and the association of their activity with licking. All subjects were implanted with a bundle of microelectrodes aimed at the NTS and allowed to recover. Following moderate water deprivation, rats were placed in an experimental chamber where tastants or artificial saliva (AS) were delivered from a lick spout. Electrophysiological responses were recorded, and waveforms from single cells were isolated offline. Results showed that only a minority of NTS cells responded to taste stimuli as determined by conventional firing-rate measures. In contrast, most cells, including taste-responsive cells, tracked the lick pattern, as evidenced by significant lick coherence in the 5- to 7-Hz range. Several quantitative measures of taste selectivity and lick relatedness showed that the population formed a continuum, ranging from cells dominated by taste responses to those dominated by lick relatedness. Moreover, even neurons whose responses were highly correlated with lick activity could convey substantial information about taste quality. In all, data point to a blurred boundary between taste-dominated and lick-related cells in NTS, suggesting that information from the taste of food and from the movements it evokes are seamlessly integrated. NEW & NOTEWORTHY Neurons in the rostral nucleus of the solitary tract (NTS) are known to encode information about taste. However, recordings from awake rats reveal that only a minority of NTS cells respond exclusively to taste stimuli. The majority of neurons track behaviors associated with food consumption, and even strongly lick-related neurons could convey information about taste quality. These findings suggest that the NTS integrates information from both taste and behavior to identify food.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sanghoon Oh ◽  
Wi Hoon Jung ◽  
Taekwan Kim ◽  
Geumsook Shim ◽  
Jun Soo Kwon

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample t-test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.


2021 ◽  
Vol 2021 (9) ◽  
pp. pdb.prot106872
Author(s):  
Ayako Yamaguchi

Understanding the neural basis of behavior is a challenging task for technical reasons. Most methods of recording neural activity require animals to be immobilized, but neural activity associated with most behavior cannot be recorded from an anesthetized, immobilized animal. Using amphibians, however, there has been some success in developing in vitro brain preparations that can be used for electrophysiological and anatomical studies. Here, we describe an ex vivo frog brain preparation from which fictive vocalizations (the neural activity that would have produced vocalizations had the brain been attached to the muscle) can be elicited repeatedly. When serotonin is applied to the isolated brains of male and female African clawed frogs, Xenopus laevis, laryngeal nerve activity that is a facsimile of those that underlie sex-specific vocalizations in vivo can be readily recorded. Recently, this preparation was successfully used in other species within the genus including Xenopus tropicalis and Xenopus victorianus. This preparation allows a variety of techniques to be applied including extracellular and intracellular electrophysiological recordings and calcium imaging during vocal production, surgical and pharmacological manipulation of neurons to evaluate their impact on motor output, and tract tracing of the neural circuitry. Thus, the preparation is a powerful tool with which to understand the basic principles that govern the production of coherent and robust motor programs in vertebrates.


2002 ◽  
Vol 88 (2) ◽  
pp. 699-714 ◽  
Author(s):  
James A. Kaltenbach ◽  
John D. Rachel ◽  
T. Alecia Mathog ◽  
Jinsheng Zhang ◽  
Pamela R. Falzarano ◽  
...  

Cisplatin causes both acute and chronic forms of tinnitus as well as increases in spontaneous neural activity (hyperactivity) in the dorsal cochlear nucleus (DCN) of hamsters. It has been hypothesized that the induction of hyperactivity in the DCN may be a consequence of cisplatin's effects on cochlear outer hair cells (OHCs); however, systematic studies testing this hypothesis have yet to appear in the literature. In the present investigation, the relationship between hyperactivity and OHC loss, induced by cisplatin, was examined in detail. Hamsters received five treatments of cisplatin at doses ranging from 1.5 to 3 mg · kg−1 · day−1, every other day. Beginning 1 mo after initiation of treatment, electrophysiological recordings were carried out on the surface of the DCN to measure spontaneous multiunit activity along a set of coordinates spanning the medial-lateral (tonotopic) axis of the DCN. After recordings, cochleas were removed and studied histologically using a scanning electron microscope. The results revealed that cisplatin-treated animals with little or no loss of OHCs displayed levels of activity similar to those seen in saline-treated controls. In contrast, the majority (75%) of cisplatin-treated animals with severe OHC loss displayed well-developed hyperactivity in the DCN. The induced hyperactivity was seen mainly in the medial (high-frequency) half of the DCN of treated animals. This pattern was consistent with the observation that OHC loss was distributed mainly in the basal half of the cochlea. In several of the animals with severe OHC loss and hyperactivity, there was no significant damage to IHC stereocilia nor any observable irregularities of the reticular lamina that might have interfered with normal IHC function. Hyperactivity was also observed in the DCN of animals showing severe losses of OHCs accompanied by damage to IHCs, although the degree of hyperactivity in these animals was less than in animals with severe OHC loss but intact IHCs. These results support the view that loss of OHC function may be a trigger of tinnitus-related hyperactivity in the DCN and suggest that this hyperactivity may be somewhat offset by damage to IHCs.


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