In the mid-19th century, a misconception was born, which understandably persists in the minds of many neuroscientists today. The eminent scientist Albert von Kölliker named a tubular-shaped piece of tissue found in the brains of all mammals studied to date, the tuberculum olfactorium – or what is commonly known as the olfactory tubercle (OT). In doing this, Kölliker ascribed “olfactory” functions and an “olfactory” purpose to the OT. The OT has since been classified as one of several olfactory cortices. However, further investigations of OT functions, especially over the last decade, have provided evidence for roles of the OT beyond olfaction, including in learning, motivated behaviors, and even seeking of psychoactive drugs. Indeed, research to date suggests caution in assigning the OT with a purely olfactory role. Here, I build on previous research to synthesize a model wherein the OT, which may be more appropriately termed the “tubular striatum” (TuS), is a neural system in which sensory information der...

Throughout daily life, we are exposed to excess information that is beyond our capacity to process. Selective attention filters out unnecessary noise and allows us to focus on relevant stimuli ([Noonan et al., 2018][1]). Research has long focused on trying to uncover the complex neural mechanisms

Through statistical learning (SL), cognitive systems may discover the underlying regularities in the environment. Testing human adults ( n = 35, 21 females), we document, in the context of a classical visual SL task, divergent rhythmic EEG activity in the interstimulus delay periods within patterns versus between patterns (i.e., pattern transitions). Our findings reveal increased oscillatory activity in the beta band (∼20 Hz) at triplet transitions that indexes learning: it emerges with increased pattern repetitions; and importantly, it is highly correlated with behavioral learning outcomes. These findings hold the promise of converging on an online measure of learning regularities and provide important theoretical insights regarding the mechanisms of SL and prediction. SIGNIFICANCE STATEMENT Statistical learning has become a major theoretical construct in cognitive science, providing the primary means by which organisms learn about regularities in the environment. As such, it is a critical building block...

GABAergic interneurons represent a heterogenous group of cell types in neocortex that can be clustered based on developmental origin, morphology, physiology, and connectivity. Two abundant populations of cortical GABAergic interneurons include the low-threshold, somatostatin (SST)-expressing cells and the fast-spiking, parvalbumin (PV)-expressing cells. While SST+ and PV+ interneurons are both early born and migrate into the developing neocortex at similar times, SST+ cells are incorporated into functional circuits prior to PV+ cells. During this early period of neural development, SST+ cells play critical roles in the assembly and maturation of other cortical circuits; however, the mechanisms underlying this process remain poorly understood. Here, using both sexes of conditional mutant mice, we discovered that SST+ interneuron-derived Collagen XIX, a synaptogenic extracellular matrix protein, is required for the formation of GABAergic, perisomatic synapses by PV+ cells. These results, therefore, identify ...

Maps of the synapses made and neurotransmitters released by all neurons in model systems, such as Caenorhabditis elegans have left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit of C. elegans as a model, we mapped which cells express each of the 26 neurotransmitter GPCRs of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. Receptor knockouts reveal few egg-laying defects under standard laboratory conditions, suggesting that the receptors function redundantly or regulate egg-laying only in specific conditions; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for under...

The subthalamic nucleus (STN) plays a key role in the control of voluntary movements and basal ganglia disorders, such as Parkinson's disease and hemiballismus. The STN receives glutamatergic inputs directly from the cerebral cortex via the cortico-STN hyperdirect pathway and GABAergic inputs from the external segment of the globus pallidus (GPe) via the cortico-striato-GPe-STN indirect pathway. The STN then drives the internal segment of the globus pallidus, which is the output nucleus of the basal ganglia. Thus, clarifying how STN neuronal activity is controlled by the two inputs is crucial. Cortical stimulation evokes early excitation and late excitation in STN neurons, intervened by a short gap. Here, to examine the origin of each component of this biphasic response, we recorded neuronal activity in the STN, combined with electrical stimulation of the motor cortices and local drug application in two male monkeys ( Macaca fuscata ) in the awake state. Local application of glutamate receptor antagonists,...

Humans adapt to mechanical perturbations such as force fields during reaching within tens of trials. However, recent findings suggested that this adaptation may start within one single trial, i.e., online corrective movements can become tuned to the unanticipated perturbations within a trial. This was highlighted in previous works with a reaching experiment in which participants had to stop at a via-point (VP) located between the start and the goal. A force field was applied during the first and second parts of the movement and then occasionally unexpectedly switched off at the VP during catch trials. The results showed an after-effect during the second part of the movement when participants exited the VP. This behavioural result was interpreted as a standard after-effect, but it remained unclear how it was related to conventional trial-by-trial learning. The current study aimed to investigate how long do such changes in movement representations last in memory. For this, we have studied the same reaching t...

Humans learn quickly which actions cause them harm. As social beings, we also need to learn to avoid actions that hurt others. It is currently unknown whether humans are as good at learning to avoid others' harm (prosocial learning) as they are at learning to avoid self-harm (self-relevant learning). Moreover, it remains unclear how the neural mechanisms of prosocial learning differ from those of self-relevant learning. In this fMRI study, 96 male human participants learned to avoid painful stimuli either for themselves or for another individual. We found that participants performed more optimally when learning for the other than for themselves. Computational modeling revealed that this could be explained by an increased sensitivity to subjective values of choice alternatives during prosocial learning. Increased value sensitivity was further associated with empathic traits. On the neural level, higher value sensitivity during prosocial learning was associated with stronger engagement of the ventromedial PF...

During aging, skeletal muscles become atrophic and lose contractile force. Aging can also impact the neuromuscular junction (NMJ), a synapse that transmits signals from motoneurons to muscle fibers to control muscle contraction. However, in contrast to muscle aging that has been studied extensively, less is known about the molecular mechanisms of NMJ aging although its structure and function are impaired in aged animals. To this end, we performed RNA sequencing (RNA-seq) analysis to identify genes whose expression in synapse-rich region is altered. Gene ontology (GO) analysis highlighted genes relating to nuclear structure or function. In particular, lamin A/C, an intermediate filament protein critical for the interphase nuclear architecture, was reduced. Remarkably, mutation of lamin A/C in muscles or motoneurons had no effect on NMJ formation in either sex of mice, but the muscle mutation caused progressive denervation, acetylcholine receptor (AChR) cluster fragmentation, and neuromuscular dysfunction. I...