What role does color play in the neural representation of complex shapes? We approached the question by measuring color responses of face-selective neurons, using fMRI-guided microelectrode recording of the middle and anterior face patches of inferior temporal cortex (IT) in rhesus macaques. Face-selective cells responded weakly to pure color (equiluminant) photographs of faces. But many of the cells nonetheless showed a bias for warm colors when assessed using images that preserved the luminance contrast relationships of the original photographs. This bias was also found for non-face-selective neurons. Fourier analysis uncovered two components: the first harmonic, accounting for most of the tuning, was biased toward reddish colors, corresponding to the L>M pole of the L-M cardinal axis. The second harmonic showed a bias for modulation between blue and yellow colors axis, corresponding to the S-cone axis. To test what role face-selective cells play in behavior, we related the information content of the neu...

The lateral geniculate nucleus (LGN) of the dorsal thalamus is the primary recipient of the two eyes’ outputs. Most LGN neurons are monocular in that they are activated by visual stimulation through only one (dominant) eye. However, there are both intrinsic connections and inputs from binocular structures to the LGN that could provide these neurons with signals originating from the other (non-dominant) eye. Indeed, previous work introducing luminance differences across the eyes or using a single-contrast stimulus showed binocular modulation for single unit activity in anesthetized macaques and multiunit activity in awake macaques. Here, we sought to determine the influence of contrast viewed by both the non-dominant and dominant eyes on LGN single-unit responses in awake macaques. To do this, we adjusted each eye’s signal strength by independently varying the contrast of stimuli presented to the two eyes. Specifically, we recorded LGN single unit spiking activity in two awake macaques while they viewed dri...

Experiments in primary culture have helped advance our understanding of the curious phenomenon of cell cycle-related neuronal death. In a differentiated postmitotic cell such as a neuron, aberrant cell cycle reentry is strongly associated with apoptosis. Indeed, in many pathologic conditions, neuronal populations at risk for death are marked by cells engaged in a cell cycle like process. The evidence for this conclusion is typically based on finding MAP2+ cells that are also positive for cell cycle-related proteins (e.g., cyclin D) or have incorporated thymidine analogs such as bromodeoxyuridine (BrdU) or 5-ethynyl-2’-deoxyuridine (EdU) into their nuclei. We now report that we and others may have partly been led astray in pursuing this line of work. Morphometric analysis of mouse embryonic cortical cultures reveals that the size of the “cycling” MAP2+ cells is significantly smaller than those of normal neurons, and their expression of MAP2 is significantly lower. This led us to ask whether, rather than rep...

Neuronal ensembles in the infralimbic cortex (IL) develop after prolonged food self-administration training. However, rats demonstrate evidence of learning the food self-administration response as early as day 1, with responding quickly increasing to asymptotic levels. Since the contribution of individual brain regions to task performance shifts over the course of training, it remains unclear whether IL ensembles are gradually formed and refined over the course of extensive operant training, or whether functionally-relevant ensembles might be recruited and formed as early as the initial acquisition of food self-administration behavior. Here, we aimed to determine the role of IL ensembles at the earliest possible point after demonstrable learning of a response-outcome association. We first allowed rats to lever press for palatable food pellets and stopped training rats once their behavior evidenced the response-outcome association (learners). We compared their food-seeking behavior and neuronal activation (...

Inhibition plays important roles in modulating the neural activities of sensory and motor systems at different levels from synapses to brain regions. To achieve coordinated movement, motor systems produce alternating contractions of antagonist muscles, whether along the body axis or within and among limbs, which often involves direct or indirect cross-inhibitory pathways. In the nematode Caenorhabditis elegans , a small network involving excitatory cholinergic and inhibitory GABAergic motoneurons generates the dorsoventral alternation of body-wall muscles that supports undulatory locomotion. Inhibition has been suggested to be necessary for backward undulation because mutants that are defective in GABA transmission exhibit a shrinking phenotype in response to a harsh touch to the head, whereas wild-type animals produce a backward escape response. Here, we demonstrate that the shrinking phenotype is exhibited by wild-type as well as mutant animals in response to harsh touch to the head or tail, but only GAB...

While it is well established that there are robust circadian rhythms of arginine vasopressin (AVP) in the cerebrospinal fluid (CSF), the route whereby the peptide reaches the CSF is not clear. A , AVP neurons constitute the largest fraction of the SCN neuronal population. Here, we show that processes of AVP-expressing SCN neurons cross the epithelium of the 3rd ventricular wall to reach the CSF (black arrows). Additionally, we report rostro-caudal differences in AVP neuron size and demonstrate that the localization of cells expressing the clock protein PER2 extend beyond the AVP population, thereby indicating that the size of this nucleus is somewhat larger than previously understood. B , Following lateral ventricle (LV) injection of cholera toxin β subunit (CTβ ; magenta) the retrograde tracer is seen in AVP neurons of the SCN, supporting the anatomical evidence that AVP neuronal processes directly contact the CSF. Arginine vasopressin (AVP) expressing neurons form the major population in the brain’s cir...

Excitatory synaptic transmission in many neurons is mediated by two coexpressed ionotropic glutamate receptor subtypes, AMPA and NMDA receptors, that differ in kinetics, ion selectivity, and voltage-sensitivity. AMPA receptors have fast kinetics and are voltage-insensitive, while NMDA receptors have slower kinetics and increased conductance at depolarized membrane potentials. Here, we report that the voltage dependency and kinetics of NMDA receptors act synergistically to stabilize synaptic integration of EPSPs across spatial and voltage domains. Simulations of synaptic integration in simplified and morphologically realistic dendritic trees revealed that the combined presence of AMPA and NMDA conductances reduce the variability of somatic responses to spatiotemporal patterns of excitatory synaptic input presented at different initial membrane potentials and/or in different dendritic domains. This moderating effect of the NMDA conductance on synaptic integration was robust across a wide range of AMPA-to-NMD...

Animal models suggest that interactions between the hippocampus and ventral tegmental area (VTA) underlie the onset and etiology of psychosis. While a large body of research has separately characterized alterations in hippocampal and VTA function in psychosis, alterations across the VTA and hippocampus have not been characterized in first-episode psychosis (FEP). As the phase of psychosis most proximal to conversion, studies specifically focused on FEP are valuable to psychosis research. Here, we characterize alterations in VTA-hippocampal interactions across male and female human participants experiencing their first episode of psychosis using resting state functional magnetic resonance imaging (rsfMRI). In comparison to age and sex matched healthy controls (HCs), FEP individuals had significantly greater VTA-hippocampal functional coupling but significantly less VTA-striatal functional coupling. Further, increased VTA-hippocampal functional coupling in FEP correlated with individual differences in psycho...

We describe an integrate-and-fire (IF) spiking neural network that incorporates spike-timing-dependent plasticity (STDP) and simulates the experimental outcomes of four different conditioning protocols that produce cortical plasticity. The original conditioning experiments were performed in freely moving non-human primates (NHPs) with an autonomous head-fixed bidirectional brain-computer interface (BCI). Three protocols involved closed-loop stimulation triggered from (1) spike activity of single cortical neurons, (2) electromyographic (EMG) activity from forearm muscles, and (3) cycles of spontaneous cortical beta activity. A fourth protocol involved open-loop delivery of pairs of stimuli at neighboring cortical sites. The IF network that replicates the experimental results consists of 360 units with simulated membrane potentials produced by synaptic inputs and triggering a spike when reaching threshold. The 240 cortical units produce either excitatory or inhibitory postsynaptic potentials (PSPs) in their ...

Recurrent seizures intensely activate GABAA receptors (GABAA-Rs), which induces transient neuronal chloride ([Cl–]i) elevations and depolarizing GABA responses that contribute to the failure of inhibition that engenders further seizures and anticonvulsant resistance. The K+-Cl– cotransporter KCC2 is responsible for Cl– extrusion and restoration of [Cl–]i equilibrium (ECl) after synaptic activity, but at the cost of increased extracellular potassium which may retard K+-Cl– extrusion, depolarize neurons, and potentiate seizures. Thus, KCC2 may either diminish or facilitate seizure activity, and both proconvulsant and anticonvulsant effects of KCC2 inhibition have been reported. It is now necessary to identify the loci of these divergent responses by assaying both the electrographic effects and the ionic effects of KCC2 manipulation. We therefore determined the net effects of KCC2 transport activity on cytoplasmic chloride elevation and Cl– extrusion rates during spontaneous recurrent ictal-like epileptiform ...