Orbitofrontal neurons acquire responses to 'valueless' Pavlovian cues during unblocking.

The orbitofrontal cortex (OFC) has been described as signaling outcome expectancies or value. Evidence for the latter comes from the studies showing that neural signals in the OFC correlate with value across features. Yet features can co-vary with value, and individual units may participate in multiple ensembles coding different features. Here we used unblocking to test whether OFC neurons would respond to a predictive cue signaling a 'valueless' change in outcome flavor. Neurons were recorded as the rats learned about cues that signaled either an increase in reward number or a valueless change in flavor. We found that OFC neurons acquired responses to both predictive cues. This activity exceeded that exhibited to a 'blocked' cue and was correlated with activity to the actual outcome. These results show that OFC neurons fire to cues with no value independent of what can be inferred through features of the predicted outcome.

Attention-related Pearce-Kaye-Hall signals in basolateral amygdala require the midbrain dopaminergic system.

BACKGROUND: Neural activity in basolateral amygdala has recently been shown to reflect surprise or attention as predicted by the Pearce-Kaye-Hall model (PKH)--an influential model of associative learning. Theoretically, a PKH attentional signal originates in prediction errors of the kind associated with phasic firing of dopamine neurons. This requirement for prediction errors, coupled with projections from the midbrain dopamine system into basolateral amygdala, suggests that the PKH signal in amygdala may depend on dopaminergic input. METHODS: To test this, we recorded single unit activity in basolateral amygdala in rats with 6-hydroxydopamine or sham lesions of the ipsilateral midbrain region. Neurons were recorded as the rats performed a task previously used to demonstrate both dopaminergic reward prediction errors and attentional signals in basolateral amygdala neurons. RESULTS: We found that neurons recorded in sham lesioned rats exhibited the same attention-related PKH signal observed in previous studies. By contrast, neurons recorded in rats with ipsilateral 6-hydroxydopamine lesions failed to show attentional signaling. CONCLUSIONS: These results indicate a linkage between the neural instantiations of the basolateral complex of the amygdala attentional signal and dopaminergic prediction errors. Such a linkage would have important implications for understanding both normal and aberrant learning and behavior, particularly in diseases thought to have a primary effect on dopamine systems, such as addiction and schizophrenia.

A perceptual representation in the frontal eye field during covert visual search that is more reliable than the behavioral report.

Neuronal activity in the frontal eye field (FEF) identifies locations of behaviorally important objects for guiding attention and eye movements. We recorded neural activity in the FEF of monkeys trained to manually turn a lever towards the location of a pop-out target of a visual search array without shifting gaze. We examined whether the reliability of the neural representation of the salient target location predicted the monkeys' accuracy of reporting target location. We found that FEF neurons reliably encoded the location of the target stimulus not only on correct trials but also on error trials. The representation of target location in FEF persisted until the manual behavioral report but did not increase in magnitude. This result suggests that, in the absence of an eye movement report, FEF encodes the perceptual information necessary to perform the task but does not accumulate this sensory evidence towards a perceptual decision threshold. These results provide physiological evidence that, under certain circumstances, accurate perceptual representations do not always lead to accurate behavioral reports and that variability in processes outside of perception must be considered to account for the variability in perceptual choice behavior.

Encoding of stimulus frequency and sensor motion in the posterior medial thalamic nucleus.

In all sensory systems, information is processed along several parallel streams. In the vibrissa-to-barrel cortex system, these include the lemniscal system and the lesser-known paralemniscal system. The posterior medial nucleus (POm) is the thalamic structure associated with the latter pathway. Previous studies suggested that POm response latencies are positively correlated with stimulation frequency and negatively correlated with response duration, providing a basis for a phase locked loop-temporal decoding of stimulus frequency. We tested this hypothesis by analyzing response latencies of POm neurons, in both awake and anesthetized rats, to vibrissae deflections at frequencies between 0.3 and 11 Hz. We found no significant, systematic correlation between stimulation frequency and the latency or duration of POm responses. We obtained similar findings from recording in awake rats, in rats under different anesthetics, and in anesthetized rats in which the reticular activating system was stimulated. These findings suggest that stimulus frequency is not reliably reflected in response latency of POm neurons. We also tested the hypothesis that POm neurons respond preferentially to sensor motion, that is, they respond to whisking in air, without contacts. We recorded from awake, head-restrained rats while monitoring vibrissae movements. All POm neurons responded to passive whisker deflections, but none responded to noncontact whisking. Thus like their counterparts in the trigeminal ganglion, POm neurons may not reliably encode whisking kinematics. These observations suggest that POm neurons might not faithfully encode vibrissae inputs to provide reliable information on vibrissae movements or contacts.

Measurements of simultaneously recorded spiking activity and local field potentials suggest that spatial selection emerges in the frontal eye field.

The frontal eye field (FEF) participates in selecting the location of behaviorally relevant stimuli for guiding attention and eye movements. We simultaneously recorded local field potentials (LFPs) and spiking activity in the FEF of monkeys performing memory-guided saccade and covert visual search tasks. We compared visual latencies and the time course of spatially selective responses in LFPs and spiking activity. Consistent with the view that LFPs represent synaptic input, visual responses appeared first in the LFPs followed by visual responses in the spiking activity. However, spatially selective activity identifying the location of the target in the visual search array appeared in the spikes about 30 ms before it appeared in the LFPs. Because LFPs reflect dendritic input and spikes measure neuronal output in a local brain region, this temporal relationship suggests that spatial selection necessary for attention and eye movements is computed locally in FEF from spatially nonselective inputs.

Cholinergic regulation of the posterior medial thalamic nucleus.

We previously showed that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incertothalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brain stem cholinergic system, which regulates sleep-wake cycles and states of vigilance. We demonstrate that cholinergic inputs facilitate POm responses to vibrissae stimulation. Activation of the cholinergic system by stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and the pedunculopontine tegmental) or by tail pinch significantly increased the magnitude of POm responses to vibrissae stimulation. Microiontophoresis of the muscarinic receptor agonist carbachol enhanced POm responses to vibrissae stimulation. Application of carbachol to an in vitro slice preparation reduced the frequency but not the amplitude of miniature inhibitory postsynaptic currents, indicating a presynaptic site of action for carbachol. We conclude that the cholinergic system facilitates POm responses by suppressing GABAergic inputs from ZI. We propose the state-dependent gating hypothesis, which asserts that differing behavioral states, regulated by the brain stem cholinergic system, modulate the flow of information through POm.

State-dependent gating of sensory inputs by zona incerta.

We have previously shown that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incerto-thalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that the cholinergic reticular activating system, implicated in regulating states of arousal, modulates ZI activity. We show that stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and pedunculopontine tegmental) results in suppression of spontaneous firing of ZI neurons. Iontophoretic application of the cholinergic agonist carbachol to ZI neurons suppresses both their spontaneous firing and their vibrissae-evoked responses. We also found that carbachol application to an in vitro slice preparation suppresses spontaneous firing of neurons in the ventral sector of ZI (ZIv). Finally, we demonstrate that the majority of ZIv neurons contain parvalbumin and project to POm. Based on these results, we present the state-dependent gating hypothesis, which states that differing behavioral states-regulated by the brain stem cholinergic system-modulate ZI activity, thereby regulating the response properties of higher-order nuclei such as POm.

Reducing the uncertainty: gating of peripheral inputs by zona incerta.

Sensory inputs are relayed to the neocortex by "first-order" thalamic nuclei, the responses of which are determined by ascending inputs from peripheral receptors. In contrast, "higher-order" thalamic nuclei respond poorly to peripheral inputs, and their responses are thought to be determined by descending cortical inputs. We tested this hypothesis by recording from neurons in the higher-order somatosensory posterior medial (POm) nucleus of narcotized rats. As reported previously, POm neurons responded to whisker stimuli with long-latency (median, 27 msec) and low-magnitude responses, consistent with cortically driven responses. However, when we suppressed inhibitory inputs from the subthalamic nucleus zona incerta (ZI), POm responses were of significantly higher magnitude and shorter latency, with many POm neurons responding at latencies consistent with ascending driving inputs from trigeminal nuclei. Our data suggest that POm comprises two neuronal populations: one population is driven by both peripheral and cortical inputs, and the second population responds only to cortical inputs. These findings demonstrate that ZI gates peripheral inputs to POm, enabling it to function both as a first-order and higher-order nucleus. Because ZI innervates all higher-order nuclei, this gating mechanism may exert similar regulation of thalamic processing in other sensory systems.

Precise temporal responses in whisker trigeminal neurons.

The ability of rats using their whiskers to perform fine tactile discrimination rivals that of humans using their fingertips. Rats must perform these discriminations rapidly and accurately while palpating the environment with their whiskers. This suggests that whisker-derived inputs produce a robust and reliable code, capable of capturing complex, high-frequency information. The first neural representation of whisker-derived stimulus information is in primary afferent neurons of the trigeminal ganglion. Here we demonstrate that there is a continuum of direction-dependent response profiles in trigeminal neurons and provide the first quantitative analysis of the encoding of complex stimuli by these neurons. We show that all classes of trigeminal ganglion neurons respond with highly reproducible temporal spike patterns to transient stimuli. Such a robust coding mechanism may allow rapid perception of complex tactile features.