Center for the Neural Basis of Cognition

Previous work has revealed a remarkably direct neural correlate of decisions in the lateral intraparietal area (LIP). Specifically, firing rate has been observed to ramp up or down in a manner resembling the accumulation of evidence for a perceptual decision reported by making a saccade into (or away from) the neuron's response field (RF). However, this link between LIP response and decision formation emerged from studies where a saccadic target was always stimulating the RF during decisions, and where the neural correlate was the averaged activity of a restricted sample of neurons. Because LIP cells are (1) highly responsive to the presence of a visual stimulus in the RF, (2) heterogeneous, and (3) not clearly anatomically segregated from large numbers of neurons that fail selection criteria, the underlying neuronal computations are potentially obscured. To address this, we recorded single neuron spiking activity in LIP during a well-studied moving-dot direction-discrimination task and manipulated whether a saccade target was present in the RF during decision-making. We also recorded from a broad sample of LIP neurons, including ones conventionally excluded in prior studies. Our results show that cells multiplex decision signals with decision-irrelevant visual signals. We also observed disparate, repeating response "motifs" across neurons that, when averaged together, resemble traditional ramping decision signals. In sum, neural responses in LIP simultaneously carry decision signals and decision-irrelevant sensory signals while exhibiting diverse dynamics that reveal a broader range of neural computations than previously entertained.

Each down stroke of an insect's wings accelerates axial airflow over the antennae. Modeling studies suggest that this can greatly enhance penetration of air and air-born odorants through the antennal sensilla thereby periodically increasing odorant-receptor interactions. Do these periodic changes result in entrainment of neural responses in the antenna and antennal lobe (AL)? Does this entrainment affect olfactory acuity? To address these questions, we monitored antennal and AL responses in the moth Manduca sexta while odorants were pulsed at frequencies from 10–72Hz, encompassing the natural wingbeat frequency. Power spectral density (PSD) analysis was used to identify entrainment of neural activity. Statistical analysis of PSDs indicates that the antennal nerve tracked pulsed odor up to 30Hz. Furthermore, at least 50% of AL local field potentials (LFPs) and between 7–25% of unitary spiking responses also tracked pulsed odor up to 30Hz in a frequency-locked manner. Application of bicuculline (200μM) abolished pulse tracking in both LFP and unitary responses suggesting that GABAA receptor activation is necessary for pulse tracking within the AL. Finally, psychophysical measures of odor detection establish that detection thresholds are lowered when odor is pulsed at 20Hz. These results suggest that AL networks can respond to the oscillatory dynamics of stimuli such as those imposed by the wing beat in a manner analogous to mammalian sniffing.

Previous work has suggested that the peptide corticotropin-releasing factor (CRF) acts to inhibit visually guided feeding in anurans, but little is known about potential targets for CRF within the subcortical visuomotor circuitry. Here we investigated the relationship between CRF neuronal organization and visual pathways in toads. CRF-immunoreactive (ir) neurons and fibers were widely distributed throughout the ventral subpallial telencephalon and hypothalamus, although few fibers were found in telencephalic areas, such as the striatum, that are known to project to the tectum in anurans. Large populations of CRF-ir cells were observed in the bed nucleus of the stria terminalis and preoptic area as well as in the ventral infundibular hypothalamus. CRF-ir neurons and fibers also were observed in several midbrain and brain stem areas. Colchicine treatment significantly enhanced CRF-ir neurons and fibers throughout the brain, and revealed CRF-ir cell groups in several brain areas (including the dorsal hypothalamus) that were not observed in untreated animals. Intrinsic CRF-immunoreactive neurons were routinely observed in cell layer 8 and sometimes in layer 6 of the optic tectum in both untreated and colchicine-treated animals. CRF was detected in toad optic tectum by radioimmunoassay, although tectal CRF content was less than that of the hypothalamus and forebrain. Unilateral eye ablation did not affect CRF content of the contralateral optic tectum. We conclude that CRF-producing neurons are widely distributed in several areas of the toad brain known to be involved in regulating the behavioral, autonomic and endocrine response to stressors, including the optic tectum and several brain areas known to project to the optic tectum. Furthermore, retinal afferents do not contribute significantly to tectal CRF content.

Each down stroke of an insect's wings accelerates axial airflow over the antennae. Modeling studies suggest that this can greatly enhance penetration of air and air-born odorants through the antennal sensilla thereby periodically increasing odorant-r.

Modern manufacturing was revolutionized by the use of interchangeable parts so similar in their function that any one could effectively replace any other. Making such parts meant that manufacturers did not need to keep track of which nut worked with which bolt or which piston was intended to go in which cylinder. Similarly, most physiological analyses ignore cell-to-cell variation and focus instead on differences between cell types, as though each cell of a specific class were functionally equivalent to any other cell of the same type.

N-methyl-D-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia. The illness is also characterized by gamma oscillatory disturbances, which can be evaluated with precise frequency specificity employing auditory cortical entrainment paradigms. This computational study investigates how synaptic NMDA hypofunction may give rise to network level oscillatory deficits as indexed by entrainment paradigms. We developed a computational model of a local cortical circuit with pyramidal cells and fast-spiking interneurons (FSI), incorporating NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA), and γ-aminobutyric acid (GABA) synaptic kinetics. We evaluated the effects of varying NMDA conductance on FSIs and pyramidal cells, as well as AMPA to NMDA ratio. We also examined the differential effects across a broad range of entrainment frequencies as a function of NMDA conductance. Varying NMDA conductance onto FSIs revealed an inverted-U relation with network gamma whereas NMDA conductance onto the pyramidal cells had a more monotonic relationship. Varying NMDA vs. AMPA conductance onto FSIs demonstrated the necessity of AMPA in the generation of gamma while NMDA receptors had a modulatory role. Finally, reducing NMDA conductance onto FSI and varying the stimulus input frequency reproduced the specific reductions in gamma range (~40 Hz) as observed in schizophrenia studies. Our computational study showed that reductions in NMDA conductance onto FSIs can reproduce similar disturbances in entrainment to periodic stimuli within the gamma range as reported in schizophrenia studies. These findings provide a mechanistic account of how specific cellular level disturbances can give rise to circuitry level pathophysiologic disturbance in schizophrenia.