Hand-Rearing Method for Infant Marmosets

The common marmoset (Callithrix jacchus) is a small and highly social New World monkey with high reproduction rates, which has been proven to be a ...

Zhejiang University

The compromised abilities to understand speech and localize sounds are two hallmark deficits in aged individuals. Earlier studies have shown that age-related deficits in cortical neural timing, which is clearly associated with speech perception, can be partially reversed with auditory training. However, whether training can reverse aged-related cortical changes in the domain of spatial processing has never been studied. In this study, we examined cortical spatial processing in ~21-month-old rats that were trained on a sound-azimuth discrimination task. We found that animals that experienced 1 month of training displayed sharper cortical sound-azimuth tuning when compared to the age-matched untrained controls. This training-induced remodeling in spatial tuning was paralleled by increases of cortical parvalbumin-labeled inhibitory interneurons. However, no measurable changes in cortical spatial processing were recorded in age-matched animals that were passively exposed to training sounds with no task demands. These results that demonstrate the effects of training on cortical spatial domain processing in the rodent model further support the notion that age-related changes in central neural process are, due to their plastic nature, reversible. Moreover, the results offer the encouraging possibility that behavioral training might be used to attenuate declines in auditory perception, which are commonly observed in older individuals.

Reversal of Age-Related Changes in Cortical Sound-Azimuth Selectivity with Training.

A striking property of the auditory system is its capacity for the stimulus-specific adaptation (SSA), which is the reduction of neural response to repeated stimuli but a recuperative response to novel stimuli. SSA is found in both the medial geniculate body (MGB) and thalamic reticular nucleus (TRN). However, it remains unknown whether the SSA of MGB neurons is modulated by inhibitory inputs from the TRN, as it is difficult to investigate using the extracellular recording method. In the present study, we performed intracellular recordings in the MGB of anesthetized guinea pigs and examined whether and how the TRN modulates the SSA of MGB neurons with inhibitory inputs. This was accomplished by using microinjection of lidocaine to inactivate the neural activity of the TRN. We found that (1) MGB neurons with hyperpolarized membrane potentials exhibited SSA at both the spiking and subthreshold levels; (2) SSA of MGB neurons depends on the interstimulus interval (ISI), where a shorter ISI results in stronger SSA; and (3) the long-lasting hyperpolarization of MGB neurons decreased after the burst firing of the TRN was inactivated. As a result, SSA of these MGB neurons was diminished after inactivation of the TRN. Taken together, our results revealed that the SSA of the MGB is strongly modulated by the neural activity of the TRN, which suggests an alternative circuit mechanism underlying the SSA of the auditory thalamus.

Stimulus-Specific Adaptation in Auditory Thalamus Is Modulated by the Thalamic Reticular Nucleus.

Temporal processing is crucial for auditory perception and cognition, especially for communication sounds. Previous studies have shown that the auditory cortex and the thalamus use temporal and rate representations to encode slowly and rapidly changing time-varying sounds. However, how the primate inferior colliculus (IC) encodes time-varying sounds at the millisecond scale remains unclear. In this study, we investigated the temporal processing by IC neurons in awake marmosets to Gaussian click trains with varying interclick intervals (2-100 ms). Strikingly, we found that 28% of IC neurons exhibited rate representation with nonsynchronized responses, which is in sharp contrast to the current view that the IC only uses a temporal representation to encode time-varying signals. Moreover, IC neurons with rate representation exhibited response properties distinct from those with temporal representation. We further demonstrated that reversible inactivation of the primary auditory cortex modulated 17% of the stimulus-synchronized responses and 21% of the nonsynchronized responses of IC neurons, revealing that cortico-colliculus projections play a role, but not a crucial one, in temporal processing in the IC. This study has significantly advanced our understanding of temporal processing in the IC of awake animals and provides new insights into temporal processing from the midbrain to the cortex.

Corticofugal modulation of temporal and rate representations in the inferior colliculus of the awake marmoset.

Cortical feedback has long been considered crucial for the modulation of sensory perception and recognition. However, previous studies have shown varying modulatory effects of the primary auditory cortex (A1) on the auditory response of subcortical neurons, which complicate interpretations regarding the function of A1 in sound perception and recognition. This has been further complicated by studies conducted under different brain states. In the current study, we used cryo-inactivation in A1 to examine the role of corticothalamic feedback on medial geniculate body (MGB) neurons in awake marmosets. The primary effects of A1 inactivation were a frequency-specific decrease in the auditory response of most MGB neurons coupled with an increased spontaneous firing rate, which together resulted in a decrease in the signal-to-noise ratio. In addition, we report for the first time that A1 robustly modulated the long-lasting sustained response of MGB neurons, which changed the frequency tuning after A1 inactivation, e.g. some neurons are sharper with corticofugal feedback and some get broader. Taken together, our results demonstrate that corticothalamic modulation in awake marmosets serves to enhance sensory processing in a manner similar to center-surround models proposed in visual and somatosensory systems, a finding which supports common principles of corticothalamic processing across sensory systems.

Selective corticofugal modulation on sound processing in auditory thalamus of awake marmosets.

The cerebellum is involved in encoding balance, posture, speed, and gravity during locomotion. However, most studies are carried out on flat surfaces, and little is known about cerebellar activity during free ambulation on slopes. Here, it has been imaged the neuronal activity of cerebellar molecular interneurons (MLIs) and Purkinje cells (PCs) using a miniaturized microscope while a mouse is walking on a slope. It has been found that the neuronal activity of vermal MLIs specifically enhanced during uphill and downhill locomotion. In addition, a subset of MLIs is activated during entire uphill or downhill positions on the slope and is modulated by the slope inclines. In contrast, PCs showed counter-balanced neuronal activity to MLIs, which reduced activity at the ramp peak. So, PCs may represent the ramp environment at the population level. In addition, chemogenetic inactivation of lobule V of the vermis impaired uphill locomotion. These results revealed a novel micro-circuit in the vermal cerebellum that regulates ambulatory behavior in 3D terrains.

Guoqiang Jia

Zhejiang University

Hand-Rearing Method for Infant Marmosets