Effects of high-fat diet and gastric bypass on neurons in the caudal solitary nucleus

Boxwell, Alison J.; Chen, Z.; Mathes, Clare M.; Spector, Alan C.; Roux, Carel W. le; Travers, Susan P.; Travers, Joseph B.

doi:10.1016/j.physbeh.2015.07.025

Cited by 7 publications

(8 citation statements)

References 82 publications

(140 reference statements)

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“…( 117 , 118 )]. Furthermore, brief access tests in rodents often did not indicate reduced avidity for sucrose or high fat and rats’ voluntary work for sucrose or lipid solutions is not decreased ( 119 – 122 ). Nonetheless, whether the findings in animal models can be directly translated into the human situation is not clear, and only few objectively assessed data in humans are available.…”

Section: Notes Of Caution On the Use Of Animal Models In Bariatric Sumentioning

confidence: 99%

The Use of Rat and Mouse Models in Bariatric Surgery Experiments

Lutz

Bueter

2016

Front. Nutr.

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Animal models have been proven to be a crucial tool for investigating the physiological mechanisms underlying bariatric surgery in general and individual techniques in particular. By using a translational approach, most of these studies have been performed in rodents and have helped to understand how bariatric surgery may or may not work. However, data from studies using animal models should always be critically evaluated for their transferability to the human physiology. It is, therefore, the aim of this review to summarize both advantages and limitations of data generated by animal based experiments designed to investigate and understand the physiological mechanisms at the root of bariatric surgery.

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Section: Notes Of Caution On the Use Of Animal Models In Bariatric Sumentioning

confidence: 99%

The Use of Rat and Mouse Models in Bariatric Surgery Experiments

Lutz

Bueter

2016

Front. Nutr.

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“…After the light modulation protocols, we assessed the presence of voltage-gated channels. The presence of I A was tested in voltage clamp by hyperpolarizing the cell from resting membrane potential to Ϫ100 mV for 1 s followed by a depolarization step for 2 s (Boxwell et al 2015). Depolarizing steps reached a maximum of Ϫ40 mV in 5-mV steps.…”

Section: Animals (Electrophysiological Experiments)mentioning

confidence: 99%

Inhibitory modulation of optogenetically identified neuron subtypes in the rostral solitary nucleus

Chen

Travers

2016

Journal of Neurophysiology

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Inhibition is presumed to play an important role in gustatory processing in the rostral nucleus of the solitary tract (rNST). One source of inhibition, GABA, is abundant within the nucleus and comes both from local, intrasolitary sources and from outside the nucleus. In addition to the receptor-mediated effects of GABA on rNST neurons, the hyperpolarization-sensitive currents, Ih and IA, have the potential to further modulate afferent signals. To elucidate the effects of GABAergic modulation on solitary tract (ST)-evoked responses in phenotypically defined rNST neurons and to define the presence of IA and Ih in the same cells, we combined in vitro recording and optogenetics in a transgenic mouse model. This mouse expresses channelrhodopsin 2 (ChR2) in GAD65-expressing GABAergic neurons throughout the rNST. GABA positive (GABA+) neurons differed from GABA negative (GABA-) neurons in their response to membrane depolarization and ST stimulation. GABA+ neurons had lower thresholds to direct membrane depolarization compared with GABA- neurons, but GABA- neurons responded more faithfully to ST stimulation. Both IA and Ih were present in subsets of GABA+ and GABA- neurons. Interestingly, GABA+ neurons with Ih were more responsive to afferent stimulation than inhibitory neurons devoid of these currents, whereas GABA- neurons with IA were more subject to inhibitory modulation. These results suggest that the voltage-gated channels underlying IA and Ih play an important role in modulating rNST output through a circuit of feedforward inhibition.

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“…The strength and kinetics of the A-type Potassium channels can be modulated in a variety of ways [ 33 – 36 ]. For example, in neurons involved in gastro-intestinal function, A-type potassium channels were modified both by diet [ 37 – 39 ] and gastric disorders [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition

et al. 2018

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Neurons process and convey information by transforming barrages of synaptic inputs into spiking activity. Synaptic inhibition typically suppresses the output firing activity of a neuron, and is commonly classified as having a subtractive or divisive effect on a neuron’s output firing activity. Subtractive inhibition can narrow the range of inputs that evoke spiking activity by eliminating responses to non-preferred inputs. Divisive inhibition is a form of gain control: it modifies firing rates while preserving the range of inputs that evoke firing activity. Since these two “modes” of inhibition have distinct impacts on neural coding, it is important to understand the biophysical mechanisms that distinguish these response profiles. In this study, we use simulations and mathematical analysis of a neuron model to find the specific conditions (parameter sets) for which inhibitory inputs have subtractive or divisive effects. Significantly, we identify a novel role for the A-type Potassium current (IA). In our model, this fast-activating, slowly-inactivating outward current acts as a switch between subtractive and divisive inhibition. In particular, if IA is strong (large maximal conductance) and fast (activates on a time-scale similar to spike initiation), then inhibition has a subtractive effect on neural firing. In contrast, if IA is weak or insufficiently fast-activating, then inhibition has a divisive effect on neural firing. We explain these findings using dynamical systems methods (plane analysis and fast-slow dissection) to define how a spike threshold condition depends on synaptic inputs and IA. Our findings suggest that neurons can “self-regulate” the gain control effects of inhibition via combinations of synaptic plasticity and/or modulation of the conductance and kinetics of A-type Potassium channels. This novel role for IA would add flexibility to neurons and networks, and may relate to recent observations of divisive inhibitory effects on neurons in the nucleus of the solitary tract.

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Effects of high-fat diet and gastric bypass on neurons in the caudal solitary nucleus

Cited by 7 publications

References 82 publications

The Use of Rat and Mouse Models in Bariatric Surgery Experiments

The Use of Rat and Mouse Models in Bariatric Surgery Experiments

Inhibitory modulation of optogenetically identified neuron subtypes in the rostral solitary nucleus

Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition

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