Distinct Firing Activities of the Hypothalamic Arcuate Nucleus Neurons to Appetite Hormones

The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control

Distinct firing activities of the hypothalamic arcuate nucleus neurons to appetite hormones

The hypothalamic arcuate nucleus (Arc) is a central unit that controls the appetite through the integration of metabolic, hormonal, and neuronal afferent inputs. Agouti-related protein (AgRP), proopiomelanocortin (POMC), and dopaminergic neurons in the Arc differentially regulate feeding behaviors in response to hunger, satiety, and appetite, respectively. At the time of writing, the anatomical and electrophysiological characterization of these three neurons has not yet been intensively explored. Here, we interrogated the overall characterization of AgRP, POMC, and dopaminergic neurons using genetic mouse models, immunohistochemistry, and whole-cell patch recordings. We identified the distinct geographical location and intrinsic properties of each neuron in the Arc with the transgenic lines labelled with cell-specific reporter proteins. Moreover, AgRP, POMC, and dopaminergic neurons had different firing activities to ghrelin and leptin treatments. Ghrelin led to the increased firing rate of dopaminergic and AgRP neurons, and the decreased firing rate of POMC. In sharp contrast, leptin resulted in the decreased firing rate of AgRP neurons and the increased firing rate of POMC neurons, while it did not change the firing rate of dopaminergic neurons in Arc. These findings demonstrate the anatomical and physiological uniqueness of three hypothalamic Arc neurons to appetite control

Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders

Phlorotannins are natural polyphenolic compounds produced by brown marine algae and are currently found in nutritional supplements. Although they are known to cross the blood–brain barrier, their neuropharmacological actions remain unclear. Here we review the potential therapeutic benefits of phlorotannins in the treatment of neurodegenerative diseases. In mouse models of Alzheimer’s disease, ethanol intoxication and fear stress, the phlorotannin monomer phloroglucinol and the compounds eckol, dieckol and phlorofucofuroeckol A have been shown to improve cognitive function. In a mouse model of Parkinson’s disease, phloroglucinol treatment led to improved motor performance. Additional neurological benefits associated with phlorotannin intake have been demonstrated in stroke, sleep disorders, and pain response. These effects may stem from the inhibition of disease-inducing plaque synthesis and aggregation, suppression of microglial activation, modulation of pro-inflammatory signaling, reduction of glutamate-induced excitotoxicity, and scavenging of reactive oxygen species. Clinical trials of phlorotannins have not reported significant adverse effects, suggesting these compounds to be promising bioactive agents in the treatment of neurological diseases. We therefore propose a putative biophysical mechanism of phlorotannin action in addition to future directions for phlorotannin research

Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models

Hearing loss is a major risk factor for tinnitus, hyperacusis, and central auditory processing disorder. Although recent studies indicate that hearing loss causes neuroinflammation in the auditory pathway, the mechanisms underlying hearing loss-related pathologies are still poorly understood. We examined neuroinflammation in the auditory cortex following noise-induced hearing loss (NIHL) and its role in tinnitus in rodent models. Our results indicate that NIHL is associated with elevated expression of proinflammatory cytokines and microglial activation-two defining features of neuroinflammatory responses-in the primary auditory cortex (AI). Genetic knockout of tumor necrosis factor alpha (TNF-alpha) or pharmacologically blocking TNF-alpha expression prevented neuroinflammation and ameliorated the behavioral phenotype associated with tinnitus in mice with NIHL. Conversely, infusion of TNF-alpha into AI resulted in behavioral signs of tinnitus in both wild-type and TNF-alpha knockout mice with normal hearing. Pharmacological depletion of microglia also prevented tinnitus in mice with NIHL. At the synaptic level, the frequency of miniature excitatory synaptic currents (mEPSCs) increased and that of miniature inhibitory synaptic currents (mIPSCs) decreased in AI pyramidal neurons in animals with NIHL. This excitatory-to-inhibitory synaptic imbalance was completely prevented by pharmacological blockade of TNF-alpha expression. These results implicate neuroinflammation as a therapeutic target for treating tinnitus and other hearing loss-related disorders.National Institute of Health [DC009259, DC014335]; Department of Defense [W81XWH-15-1-0028, W81XWH-15-1-0356, W81XWH-15-1-0357]; Food and Health Bureau of Hong Kong Special Administrative Region Government [04150076]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Intrinsic Biophysical Properties of Frog Central Auditory Neurons

154 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008.The goal of my research is to gain insight into the intrinsic biophysical characteristics of frog central auditory neurons. For this, I utilized in vitro preparations to investigate various basic membrane properties of neurons in three major auditory centers, the dorsal medullary nucleus (DMN), the torus semicircularis (TS), and the auditory thalamus. In the second chapter, I showed that the membrane properties of DMN neurons are heterogeneous---they show diverse biophysical phenotypes (which can be characterized by the different temporal discharge patterns in response to depolarization current injections) as well as morphological phenotypes. The majority of DMN neurons are onset or transient-chopper phenotypes that are capable of encoding rapid time-varying signals. In the third chapter, I showed that TS neurons also display many different biophysical phenotypes; some of which are similar to those seen in the DMN but others are novel. This finding sheds light into their potential roles in creation of unit-specific AM rate sensitivity (or tone-induced oscillatory discharges). In the fourth chapter, I found that auditory thalamic neurons are homogeneous, showing high membrane input resistance and long time constant, and uniformly sustained-chopper temporal discharge patterns in response to depolarization currents---unlike the various phenotypes in the lower auditory brainstem the thalamic neurons cannot follow fast or slow trains of depolarization current pulses. The above findings suggest that the intrinsic biophysical characteristics of neurons likely play a role in the transformation of AM-following response along the ascending auditory pathway.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Intrinsic Biophysical Properties of Frog Central Auditory Neurons

154 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008.The goal of my research is to gain insight into the intrinsic biophysical characteristics of frog central auditory neurons. For this, I utilized in vitro preparations to investigate various basic membrane properties of neurons in three major auditory centers, the dorsal medullary nucleus (DMN), the torus semicircularis (TS), and the auditory thalamus. In the second chapter, I showed that the membrane properties of DMN neurons are heterogeneous---they show diverse biophysical phenotypes (which can be characterized by the different temporal discharge patterns in response to depolarization current injections) as well as morphological phenotypes. The majority of DMN neurons are onset or transient-chopper phenotypes that are capable of encoding rapid time-varying signals. In the third chapter, I showed that TS neurons also display many different biophysical phenotypes; some of which are similar to those seen in the DMN but others are novel. This finding sheds light into their potential roles in creation of unit-specific AM rate sensitivity (or tone-induced oscillatory discharges). In the fourth chapter, I found that auditory thalamic neurons are homogeneous, showing high membrane input resistance and long time constant, and uniformly sustained-chopper temporal discharge patterns in response to depolarization currents---unlike the various phenotypes in the lower auditory brainstem the thalamic neurons cannot follow fast or slow trains of depolarization current pulses. The above findings suggest that the intrinsic biophysical characteristics of neurons likely play a role in the transformation of AM-following response along the ascending auditory pathway.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Failed stabilization for long-term potentiation in the auditory cortex of FMR1 knockout mice.

Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1) gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP) is impaired in the developing auditory cortex of the Fmr1 knockout (KO) mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development

Distinct kinetics of inhibitory currents in thalamocortical neurons that arise from dendritic or axonal origin.

Thalamocortical neurons in the dorsal lateral geniculate nucleus (dLGN) transfer visual information from retina to primary visual cortex. This information is modulated by inhibitory input arising from local interneurons and thalamic reticular nucleus (TRN) neurons, leading to alterations of receptive field properties of thalamocortical neurons. Local GABAergic interneurons provide two distinct synaptic outputs: axonal (F1 terminals) and dendritic (F2 terminals) onto dLGN thalamocortical neurons. By contrast, TRN neurons provide only axonal output (F1 terminals) onto dLGN thalamocortical neurons. It is unclear if GABAA receptor-mediated currents originating from F1 and F2 terminals have different characteristics. In the present study, we examined multiple characteristics (rise time, slope, halfwidth and decay τ) of GABAA receptor-mediated miniature inhibitory postsynaptic synaptic currents (mIPSCs) originating from F1 and F2 terminals. The mIPSCs arising from F2 terminals showed slower kinetics relative to those from F1 terminals. Such differential kinetics of GABAAR-mediated responses could be an important role in temporal coding of visual signals