Unraveling the role of Slc10a4 in auditory processing and sensory motor gating: Implications for neuropsychiatric disorders?

Background: Psychiatric disorders, such as schizophrenia, are complex and challenging to study, partly due to the lack of suitable animal models. However, the absence of the Slc10a4 gene, which codes for a monoaminergic and cholinergic associated vesicular transporter protein, in knockout mice (Slc10a4), leads to the accumulation of extracellular dopamine. A major challenge for studying schizophrenia is the lack of suitable animal models that accurately represent the disorder.

Alterations of auditory sensory gating in mice with noise-induced tinnitus treated with nicotine and cannabis extract.

Tinnitus is a phantom sound perception affecting both auditory and limbic structures. The mechanisms of tinnitus remain unclear and it is debatable whether tinnitus alters attention to sound and the ability to inhibit repetitive sounds, a phenomenon also known as auditory gating. Here we investigate if noise exposure interferes with auditory gating and whether natural extracts of cannabis or nicotine could improve auditory pre-attentional processing in noise-exposed mice.

Loud noise-exposure changes the firing frequency of subtypes of layer 5 pyramidal neurons and Martinotti cells in the mouse auditory cortex.

Introduction: Loud noise-exposure can generate noise-induced tinnitus in both humans and animals. Imaging and studies show that noise exposure affects the auditory cortex; however, cellular mechanisms of tinnitus generation are unclear.

Methods: Here we compare membrane properties of layer 5 (L5) pyramidal cells (PCs) and Martinotti cells expressing the cholinergic receptor nicotinic alpha 2 subunit gene () of the primary auditory cortex (A1) from control and noise-exposed (4-18 kHz, 90 dB, 1.

Decreasing dorsal cochlear nucleus activity ameliorates noise-induced tinnitus perception in mice.

Background: The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca/Calmodulin kinase 2 α (CaMKII α)-positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus.

Using Cortical Neuron Markers to Target Cells in the Dorsal Cochlear Nucleus.

The dorsal cochlear nucleus (DCN) is a region of particular interest for auditory and tinnitus research. However, lack of useful genetic markers for manipulations hinders elucidation of the DCN contribution to tinnitus pathophysiology. This work assesses whether adeno-associated viral vectors (AAV) containing the calcium/calmodulin-dependent protein kinase 2α (CaMKIIα) promoter and a mouse line of nicotinic acetylcholine receptor α2 subunit (Chrna2)-Cre can target specific DCN populations.