Maintenance of optogenetic channel rhodopsin (ChR2) function in aging mice: Implications for pharmacological studies of inhibitory synaptic transmission, quantal content, and calcium homeostasis.

Disruption of synaptic function is believed to represent a common pathway contributing to cognitive decline during aging. Optogenetics is a prodigious tool for studying relationships between function and synaptic circuitry but models utilizing viral vectors present limitations. Careful characterization of the functionality of channel rhodopsin in transgenic models is crucial for determining whether they can be used across aging.

Late-Onset, Short-Term Intermittent Fasting Reverses Age-Related Changes in Calcium Buffering and Inhibitory Synaptic Transmission in Mouse Basal Forebrain Neurons.

Aging is often associated with cognitive decline and recurrent cellular and molecular impairments. While life-long caloric restriction (CR) may delay age-related cognitive deterioration as well as the onset of neurologic disease, recent studies suggest that late-onset, short-term intermittent fasting (IF), may show comparable beneficial effects as those of life-long CR to improve brain health. We used a new optogenetic aging model to study the effects of late-onset (>18 months), short-term (four to six weeks) IF on age-related changes in GABAergic synaptic transmission, intracellular calcium (Ca) buffering, and cognitive status.

Amitriptyline Decreases GABAergic Transmission in Basal Forebrain Neurons Using an Optogenetic Model of Aging.

The antidepressant drug amitriptyline is used in the treatment of clinical depression and a variety of neurological conditions such as anxiety, neuropathic pain disorders and migraine. Antidepressants are associated with both therapeutic and untoward effects, and their use in the elderly has tripled since the mid-1990s. Because of this widespread use, we are interested in testing the acute effects of amitriptyline on synaptic transmission at therapeutic concentrations well below those that block voltage-gated calcium channels.