Parvalbumin-Expressing Inhibitory Interneurons in Auditory Cortex Are Well-Tuned for Frequency

Progressive negative behavioral changes in normal aging are paralleled by a complex series of physical and functional declines expressed in the cerebral cortex. In studies conducted in the auditory domain, these degrading physical and functional cortical changes have been shown to be broadly reversed by intensive progressive training that improves the spectral and temporal resolution of acoustic inputs and suppresses behavioral distractors. Here we found older rats that were intensively trained on an attentionally demanding modulation-rate recognition task in young adulthood substantially retained training-driven improvements in temporal rate discrimination abilities over a subsequent 18-mo epoch-that is, forward into their older age. In parallel, this young-adult auditory training enduringly enhanced temporal and spectral information processing in their primary auditory cortices (A1). Substantially greater numbers of parvalbumin-and somatostatin-labeled inhibitory neurons (closer to the numbers recorded in young vigorous adults) were recorded in the A1 and hippocampus in old trained versus untrained age-matched rats. These results show that a simple form of training in young adulthood in this rat model enduringly delays the otherwise expected deterioration of the physical status and functional operations of the auditory nervous system, with evident training impacts generalized to the hippocampus.aging | auditory cortex | behavioral training | cortical processing | inhibition A degradation of the status of physical brain machinery, expressed by a decline in its temporal processing abilities, has been repeatedly associated with its deteriorating functional status in normal aging (1-4). Recent studies have shown that the machinery that supports processing accuracy and speed, as well as the processes supporting attention control and distractor suppression, can be substantially rejuvenated via simple forms of intensive training in the aged-rat model (4, 5). With auditory perceptual training, in parallel with recovery in behavioral abilities to that matching young-animal performance levels, serials of key physical, chemical, and functional aspects of cortical processing machinery in the trained rats were shown to be restored to a physical or functional status that approached that normally recorded in vigorous young-adult animals.In human studies, substantial changes in speed of processing (SOP) and in other spectro-temporal (or spatiotemporal) signal resolution of performance abilities have been shown to result from attention-demanding, speed-challenged auditory (3, 5-7) or visual training (8-11). For example, the accurate behavioral identification and stimulus-order reconstruction of rapidly successive auditory stimuli was restored in human individuals trained in their eighth decade of life to a performance level normally typifying human performance abilities recorded in their third or fourth decade (3, 6).Our goal here was to define the magnitude and endurance of an intense dose of attention-demanding modulation di...

Section: Discussionmentioning

confidence: 99%

Positive impacts of early auditory training on cortical processing at an older age

Cheng

Jia

Zhang

et al. 2017

“…PV + neurons in auditory cortex are believed to be involved in regulating the temporal precision of cortical responses instead of shaping frequency tuning, because they usually have faster response latencies and are well tuned for frequency (48). This result may explain the observation that, although training renormalized A1 temporal responses of CTM-exposed rats, it did not restore cortical frequency selectivity to normal.…”

Section: Discussionmentioning

confidence: 99%

Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure

Zhou

Darling

et al. 2015

Abnormal cortical circuitry and function as well as distortions in the modulatory neurological processes controlling cortical plasticity have been argued to underlie the origin of autism. Here, we chemically distorted those processes using an antidepressant drugexposure model to generate developmental neurological distortions like those characteristics expressed in autism, and then intensively trained altered young rodents to evaluate the potential for neuroplasticity-driven renormalization. We found that young rats that were injected s.c. with the antidepressant citalopram from postnatal d 1-10 displayed impaired neuronal repetition-rate following capacity in the primary auditory cortex (A1). With a focus on recovering grossly degraded auditory system processing in this model, we showed that targeted temporal processing deficits induced by early-life antidepressant exposure within the A1 were almost completely reversed through implementation of a simple behavioral training strategy (i.e., a modified go/no-go repetition-rate discrimination task). Degraded parvalbumin inhibitory GABAergic neurons and the fast inhibitory actions that they control were also renormalized by training. Importantly, antidepressant-induced degradation of serotonergic and dopaminergic neuromodulatory systems regulating cortical neuroplasticity was sharply reversed. These findings bear important implications for neuroplasticitybased therapeutics in autistic patients.autism | behavioral training | cortical network | antidepressant exposure | recovery of function R ecently, extensive efforts have been made to understand better the etiology of pervasive developmental disorders (PDDs), such as autism spectrum disorders (ASDs), with an ultimate goal of identifying preventive and more effective treatment strategies. At present, a general consensus from both human and animal studies is that a variety of genetic and environmental factors play an integrated role in the establishment of neurobehavioral abnormalities marking these disorders (1-5). Given the complexity of its origins and of the expressions of neurological abnormalities in ASD, it has been generally concluded that no single drug or therapy can be expected to provide effective treatment for the core and associated symptoms of ASDs (6-9).Interestingly, early behavioral intervention has been associated with significant improvements in intelligence quotient, language acquisition, and adaptive behavior (10). Furthermore, positive outcomes of individuals with an unequivocal history of moderate-severe ASD (11) provide hope that the strong behavioral deficits expressed in the disorder might, on some corrective neurobehavioral path, be reversible. What is that path? A critical question to answer is whether and to what extent the cortical network dysfunction and the subcortical machinery that regulates it, repeatedly described as distorted in humans with autism and in animal models of autism (12-15), can be reversed, either through drug treatment or via behavioral approaches.Cortical circuit mi...

“…For PV-PV mice, data were collected using either 445-nm or 520-nm wavelength light to control for nonspecific wavelength effects. Analyses were limited to well-isolated putative pyramidal neurons [see SI Methods for interneuron exclusion criteria and cluster isolation metrics (52)(53)(54)]. Mean firing rates were calculated for each 5-min interval and were analyzed using paired t tests.…”

Section: Methodsmentioning

confidence: 99%

Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

Weible

Piscopo

Rothbart

et al. 2017

Meditation training induces changes at both the behavioral and neural levels. A month of meditation training can reduce selfreported anxiety and other dimensions of negative affect. It also can change white matter as measured by diffusion tensor imaging and increase resting-state midline frontal theta activity. The current study tests the hypothesis that imposing rhythms in the mouse anterior cingulate cortex (ACC), by using optogenetics to induce oscillations in activity, can produce behavioral changes. Mice were randomly assigned to groups and were given twenty 30-min sessions of light pulses delivered at 1, 8, or 40 Hz over 4 wk or were assigned to a no-laser control condition. Before and after the month all mice were administered a battery of behavioral tests. In the light/dark box, mice receiving cortical stimulation had more light-side entries, spent more time in the light, and made more vertical rears than mice receiving rhythmic cortical suppression or no manipulation. These effects on light/dark box exploratory behaviors are associated with reduced anxiety and were most pronounced following stimulation at 1 and 8 Hz. No effects were seen related to basic motor behavior or exploration during tests of novel object and location recognition. These data support a relationship between lower-frequency oscillations in the mouse ACC and the expression of anxiety-related behaviors, potentially analogous to effects seen with human practitioners of some forms of meditation.ne month of integrated mind body meditation (1), a form of mindfulness meditation, has been shown to reduce selfreported anxiety as measured by the Profile of Mood States, reduce the stress hormone cortisol, increase ventral anterior cingulate cortex (ACC) activity, and change the white matter pathways surrounding the ACC as measured by increased fractional anisotropy in diffusion tensor imaging studies (1-4). How might a purely mental exercise such as paying attention to the present moment work to produce these changes in behavior and brain connectivity (5)?Some of these changes, including those to white matter, were hypothesized to be related to the finding that meditation can increase frontal theta activity even when the person is at rest (6). The theta activity may increase the number of active oligodendrocytes leading to increased myelination, thereby improving connectivity between the ACC and other limbic areas. Moreover, theta activity in humans has been uniquely correlated with glucose metabolism in the ACC (7). Because the ventral ACC connects to the amygdala and is thought to regulate its activity (8), these changes in the brain could result in the reduced anxiety found following meditation training.To test this idea, we developed a mouse model in which various frequencies of oscillatory activity were induced in the ACC using optogenetics. Because mindfulness meditation has often been associated with reductions in anxiety and negative affect (9), we examined exploratory behavior in the light/dark box. In this ethological model of anxiet...