The cerebellum has the reputation of being a primitive part of the brain that mostly is involved in motor coordination and motor control. Older lesion studies and more recent electrophysiological studies have, however, indicated that it is involved in temporal perception and temporal expectation building. An outstanding question is whether this temporal expectation building cerebellar activity has functional relevance. In this study, we collected magnetoencephalographic data from 30 healthy participants performing a detection task on at-threshold stimulation that was presented at the end of a sequence of temporally regular or irregular above-threshold stimulation. We found that behavioral detection rates depended on the degree of irregularity in the sequence preceding it. We also found cerebellar responses evoked by above-threshold and at-threshold stimulation. The evoked responses to at-threshold stimulation differed significantly, depending on whether it was preceded by a regular or an irregular sequence...

Interneuron loss is a prominent feature of temporal lobe epilepsy in both animals and humans and is hypothesized to be critical for epileptogenesis. As loss occurs concurrently with numerous other potentially proepileptogenic changes, however, the impact of interneuron loss in isolation remains unclear. For the present study, we developed an intersectional genetic approach to induce bilateral diphtheria toxin-mediated deletion of Vgat-expressing interneurons from dorsal and ventral hippocampus. In a separate group of mice, the same population was targeted for transient neuronal silencing with DREADDs. Interneuron ablation produced dramatic seizure clusters and persistent epileptiform activity. Surprisingly, after 1 week seizure activity declined precipitously and persistent epileptiform activity disappeared. Occasional seizures (≈1/day) persisted to the end of the experiment at 4 weeks. In contrast to the dramatic impact of interneuron ablation, transient silencing produced large numbers of interictal spik...

This systematic review presented a comprehensive survey of studies that applied transcranial magnetic stimulation and transcranial electrical stimulation to parietal and nonparietal areas to examine the neural basis of symbolic arithmetic processing. All findings were compiled with regard to the three assumptions of the triple-code model (TCM) of number processing. Thirty-seven eligible manuscripts were identified for review (33 with healthy participants and 4 with patients). Their results are broadly consistent with the first assumption of the TCM that intraparietal sulcus both hold a magnitude code and engage in operations requiring numerical manipulations such as subtraction. However, largely heterogeneous results conflicted with the second assumption of the TCM that the left angular gyrus subserves arithmetic fact retrieval, such as the retrieval of rote-learned multiplication results. Support is also limited for the third assumption of the TCM, namely, that the posterior superior parietal lobule engag...

Neuroscience research demands focused attention built upon a foundational knowledge that can encompass the full sweep of science and engineering including, among other disciplines, psychology, biology, chemistry, physics, and computer science. Neuroscience studies range from evolution of life-forms to new innovations in computational modeling. Neuroscientists can look at the population-level behavior, activity of the human brain, or atomic-level resolution of essential molecules. And yet, within these depths of emerging knowledge, the neuroscience community has the capacity to share what we know with young people and the public at large. Even little actions of communicating science in a manner that is broadly accessible and fun can initiate that ripple effect that informs a young mind. Television and social media are dominated with advertisements for online shopping, insurance companies, and cell phone plans (Statista, 2022). Furthermore, a number of mental health advertising campaigns are on the rise. Ma...

The inferior colliculus (IC), the midbrain auditory integration center, analyzes information about social vocalizations and provides substrates for higher level processing of vocal signals. We used multichannel recordings to characterize and localize responses to social vocalizations and synthetic stimuli within the IC of female and male mice, both urethane anesthetized and unanesthetized. We compared responses to ultrasonic vocalizations (USVs) with other vocalizations in the mouse repertoire and related vocal responses to frequency tuning, IC subdivisions, and sex. Responses to lower frequency, broadband social vocalizations were widespread in IC, well represented throughout the tonotopic axis, across subdivisions, and in both sexes. Responses to USVs were much more limited. Although we observed some differences in tonal and vocal responses by sex and subdivision, representations of vocal responses by sex and subdivision were largely the same. For most units, responses to vocal signals occurred only when...

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by intrusive obsessive thoughts and compulsive behaviors. Multiple studies have shown the association of polymorphisms in the SLC1A1 gene with OCD. The most common of these OCD-associated polymorphisms increases the expression of the encoded protein, excitatory amino acid transporter 3 (EAAT3), a neuronal glutamate transporter. Previous work has shown that increased EAAT3 expression results in OCD-relevant behavioral phenotypes in rodent models. In this study, we created a novel mouse model with targeted, reversible overexpression of Slc1a1 in forebrain neurons. The mice do not have a baseline difference in repetitive behavior but show increased hyperlocomotion following a low dose of amphetamine (3 mg/kg) and increased stereotypy following a high dose of amphetamine (8 mg/kg). We next characterized the effect of amphetamine on striatal cFos response and found that amphetamine increased cFos throughout the striatum in ...

As the global elderly population grows, age-related cognitive decline is becoming an increasingly significant healthcare issue, often leading to various neuropsychiatric disorders. Among the many molecular players involved in memory, AMPA-type glutamate receptors are known to regulate learning and memory, but how their dynamics change with age and affect memory decline is not well understood. Here, we examined the in vivo properties of the AMPA-type glutamate receptor GLR-1 in the AVA interneuron of the Caenorhabditis elegans nervous system during physiological aging. We found that both total and membrane-bound GLR-1 receptor levels decrease with age in wild-type worms, regardless of their location along the axon. Using fluorescence recovery after photobleaching, we also demonstrated that a reduction in GLR-1 abundance correlates with decreased local, synaptic GLR-1 receptor dynamics. Importantly, we found that reduced GLR-1 levels strongly correlate with the age-related decline in short-term associative m...

Long-term programmed rheostatic changes in physiology are essential for animal fitness. Hypothalamic nuclei and the pituitary gland govern key developmental and seasonal transitions in reproduction. The aim of this study was to identify the molecular substrates that are common and unique to developmental and seasonal timing. Adult and juvenile quail were collected from reproductively mature and immature states, and key molecular targets were examined in the mediobasal hypothalamus (MBH) and pituitary gland. qRT-PCR assays established deiodinase type 2 ( DIO2 ) and type 3 ( DIO3 ) expression in adults changed with photoperiod manipulations. However, DIO2 and DIO3 remain constitutively expressed in juveniles. Pituitary gland transcriptome analyses established that 340 transcripts were differentially expressed across seasonal photoperiod programs and 1,189 transcripts displayed age-dependent variation in expression. Prolactin ( PRL ) and follicle-stimulating hormone subunit beta ( FSHβ ) are molecular markers...

The medial mammillary bodies (MBs) play an important role in the formation of spatial memories; their dense inputs from hippocampal and brainstem regions makes them well placed to integrate movement-related and spatial information, which is then extended to the anterior thalamic nuclei and beyond to the cortex. While the anatomical connectivity of the medial MBs has been well studied, much less is known about their physiological properties, particularly in freely moving animals. We therefore carried out a comprehensive characterization of medial MB electrophysiology across arousal states by concurrently recording from the medial MB and the CA1 field of the hippocampus in male rats. In agreement with previous studies, we found medial MB neurons to have firing rates modulated by running speed and angular head velocity, as well as theta-entrained firing. We extended the characterization of MB neuron electrophysiology in three key ways: (1) we identified a subset of neurons (25%) that exhibit dominant bursting...

Proprioception, the sense of limb and body position, is required to produce accurate and precise movements. Proprioceptive sensory neurons transmit muscle length and tension information to the spinal cord. The function of excitatory neurons in the intermediate spinal cord, which receive this proprioceptive information, remains poorly understood. Using genetic labeling strategies and patch-clamp techniques in acute spinal cord preparations in mice, we set out to uncover how two sets of spinal neurons, Clarke's column (CC) and Atoh1 -lineage neurons, respond to electrical activity and how their inputs are organized. Both sets of neurons are located in close proximity in laminae V–VII of the thoracolumbar spinal cord and have been described to receive proprioceptive signals. We find that a majority of CC neurons have a tonic-firing type and express a distinctive hyperpolarization-activated current (Ih). Atoh1 -lineage neurons, which cluster into two spatially distinct populations, are mostly a fading-firing t...