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...

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...

Phase entrainment of cells by theta oscillations is thought to globally coordinate the activity of cell assemblies across different structures, such as the hippocampus and neocortex. This coordination is likely required for optimal processing of sensory input during recognition and decision-making processes. In quadruple-area ensemble recordings from male rats engaged in a multisensory discrimination task, we investigated phase entrainment of cells by theta oscillations in areas along the corticohippocampal hierarchy: somatosensory barrel cortex (S1BF), secondary visual cortex (V2L), perirhinal cortex (PER), and dorsal hippocampus (dHC). Rats discriminated between two 3D objects presented in tactile-only, visual-only, or both tactile and visual modalities. During task engagement, S1BF, V2L, PER, and dHC LFP signals showed coherent theta-band activity. We found phase entrainment of single-cell spiking activity to locally recorded as well as hippocampal theta activity in S1BF, V2L, PER, and dHC. While phase ...

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...

The avian telencephalic structure nidopallium caudolaterale (NCL) functions as an analog to the mammalian prefrontal cortex. In crows, corvid songbirds, it plays a crucial role in higher cognitive and executive functions. These functions rely on the NCL's extensive telencephalic connections. However, systematic investigations into the brain-wide connectivity of the NCL in crows or other songbirds are lacking. Here, we studied its input and output connections by injecting retrograde and anterograde tracers into the carrion crow NCL. Our results, mapped onto a published carrion crow brain atlas, confirm NCL multisensory connections and extend prior pigeon findings by identifying a novel input from the hippocampal formation. Furthermore, we analyze crow NCL efferent projections to the arcopallium and report newly identified arcopallial neurons projecting bilaterally to the NCL. These findings help to clarify the role of the NCL as central executive hub in the corvid songbird brain.

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...

Vocalization, a means of social communication, is prevalent among many species, including humans. Both rats and mice use ultrasonic vocalizations (USVs) in various social contexts and affective states. The motor cortex is hypothesized to be involved in precisely controlling USVs through connections with critical regions of the brain for vocalization, such as the periaqueductal gray matter (PAG). However, it is unclear how neurons in the motor cortex are modulated during USVs. Moreover, the relationship between USV modulation of neurons and anatomical connections from the motor cortex to PAG is also not clearly understood. In this study, we first characterized the activity patterns of neurons in the primary and secondary motor cortices during emission of USVs in rats using large-scale electrophysiological recordings. We also examined the axonal projection of the motor cortex to PAG using retrograde labeling and identified two clusters of PAG-projecting neurons in the anterior and posterior parts of the moto...