Lamotrigine (LTG) is generally considered as a voltage-gated sodium (Nav) channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs), powerfully inhibit granule c...

Circadian rhythmicity in mammals is generated by a pair of nuclei in the anterior hypothalamus known as the suprachiasmatic nuclei (SCN), whose neurons express a variety of neuropeptides that are thought to play an important role in the circadian timing system. To evaluate the influence of VIP on inhibitory synaptic transmission between SCN neurons, we used whole cell patch-clamp recording in a...

Peripheral nerve injury promotes the release of brain-derived neurotrophic factor (BDNF) from spinal microglial cells and primary afferent terminals. This induces an increase in dorsal horn excitability that contributes to "central sensitization" and to the onset of neuropathic pain. Although it is accepted that impairment of GABAergic and/or glycinergic inhibition contributes to this process, ...

Temporal lobe epilepsy is associated with loss of interneurons and inhibitory dysfunction in the dentate gyrus. While status epilepticus (SE) leads to changes in granule cell inhibition, whether dentate basket cells critical for regulating granule cell feedforward and feedback inhibition express tonic GABA currents (I(GABA)) and undergo changes in inhibition after SE is not known. We find that ...

21 Olfactory bulb (OB) glomeruli, the initial sites of synaptic processing of odor information, 22 exhibit high levels of nicotinic acetylcholine receptor (nAChR) expression and receive strong 23 cholinergic input from the basal forebrain. The role of glomerular nAChRs in olfactory 24 processing, however, remains to be elucidated. External tufted (ET) cells are a major source of 25 excitation i...

Chronic use of alcohol is associated with structural and functional alterations in brain areas that subserve cognitive processes. Of particular importance is the prefrontal cortex (PFC) that is involved in higher order behaviors such as decision making, risk assessment and judgment. Understanding the mechanisms that underlie alcohol's effects on PFC function is important for developing strategi...

We previously reported that orexin neurons are directly hyperpolarized by noradrenaline (NA) and dopamine. In the present study, we show that NA, dopamine and adrenaline all directly hyperpolarized orexin neurons. This response was inhibited by the α2 adrenergic receptor (α2-AR) antagonist, idazoxan or BRL44408, and was mimicked by the α2-AR selective agonist, UK14304. A low concentration of Ba...

After unilateral peripheral vestibular lesions, the brain plasticity underlying early recovery from the static symptoms is not fully understood. Principal cells of the chick tangential nucleus offer a subset of morphologically defined vestibular nuclei neurons to study functional changes after vestibular lesions. Chickens show posture and balance deficits immediately after unilateral vestibular...

Principal cells of the chick tangential nucleus are vestibular nucleus neurons in the hindbrain. Although detailed information is available on the morphogenesis of principal cells and synaptogenesis of primary vestibular fibers, this is the first study of their early functional development, when vestibular terminals emerge at embryonic days 10 and 13 (E10 and E13). At E10, 60% of principal cell...

In the cerebellum, the basket cell innervation on Purkinje cells provides a major GABAergic inhibitory control of the single efferent output from the cerebellum. The Shaker-type K channel Kv1.1 is localized at the axon arborization preceding the terminal of the basket cells and is therefore a potential candidate for regulating the GABAergic inhibition. In this study, we directly assess this rol...