Stimulus-induced reduction of noise correlation in rat prefrontal cortex.

We have shown previously that stimulus-induced modulation of noise correlation in rat somatosensory cortex conveys additional information about the delivery of tactile stimulation. Here we investigated whether noise correlation is also modulated by an external sensory stimulus in rat prefrontal cortex and, if so, whether such modulation conveys additional information on stimulus delivery. Noise correlation was significantly reduced after the onset of a conditional stimulus (auditory tone) that signaled an electric foot shock in the prefrontal cortex. However, noise correlation contributed little to the transmission of information on stimulus delivery. These results indicate that a meaningful sensory stimulus reduces noise correlation in rat prefrontal cortex, but such modulation does not play a significant role in conveying information on stimulus delivery.

Putative γ-aminobutyric acid neurons in the ventral tegmental area have a similar pattern of plasticity as dopamine neurons during appetitive and aversive learning.

Dopamine influences affective, motor and cognitive processing, and multiple forms of learning and memory. This multifaceted functionality, which operates across long temporal windows, is broader than the narrow and temporally constrained role often ascribed to dopamine neurons as reward prediction error detectors. Given the modulatory nature of dopamine neurotransmission, that dopamine release is activated by both aversive and appetitive stimuli, and that dopamine receptors are often localized extrasynaptically, a role for dopamine in transmitting precise error signals has been questioned. Here we recorded from ventral tegmental area (VTA) neurons, while exposing rats to novel stimuli that were predictive of an appetitive or aversive outcome in the same behavioral session. The VTA contains dopamine and -aminobutyric acid (GABA) neurons that project to striatal and cortical regions and are strongly implicated in learning and affective processing. The response of VTA neurons, regardless of whether they had putative dopamine or GABA waveforms, transformed flexibly as animals learned to associate novel stimuli from different sensory modalities to appetitive or aversive outcomes. Learning the appetitive association led to larger excitatory VTA responses, whereas acquiring the aversive association led to a biphasic response of brief excitation followed by sustained inhibition. These responses shifted rapidly as outcome contingencies changed. These data suggest that VTA neurons interface sensory information with representational memory of aversive and appetitive events. This pattern of plasticity was not selective for putative dopamine neurons and generalized to other cells, suggesting that the temporally precise information transfer from the VTA may be mediated by faster acting GABA neurons.

Anterior cingulate neurons represent errors and preparatory attention within the same behavioral sequence.

The anterior cingulate cortex (ACC) has been implicated in both preparatory attention (i.e., selecting behaviorally relevant stimuli) and in detecting errors. We recorded from the rat ACC and medial prefrontal cortex (mPFC), which is functionally homologous to the primate dorsolateral PFC, during an attention task. The three-choice serial reaction time task requires a rat to orient toward and divide attention between three brief (300 ms duration) light stimuli presented in random order across nose poke holes in an operant chamber. In both the ACC and mPFC, we found that neural activity was related to the level of preparatory (precue) attention and subsequent correct or incorrect choice, in that the magnitude of the single units' response to the cue was lower on incorrect trials and was not different than baseline on unattended trials. This preparatory neural activity consisted of both excitatory and inhibitory phasic responses. The number of units responding to the cue was similarly graded, in that fewer units exhibited phasic responses to the cue on incorrect and unattended trials, compared with correct trials. Although preparatory activity was found in both the ACC and mPFC, activity after incorrect nose pokes, which may be related to error detection, were only observed in the ACC. Thus, during the same behavioral sequence, the ACC encodes both error-related events and preparatory attention, whereas the mPFC only participates in preparatory attention. The finding of substantial inhibitory activity during the preparatory period suggests a critical role for inhibition of pyramidal cells in PFC-mediated cognitive functions.

Plasticity and memory in the prefrontal cortex.

Neuropsychological and neuroimaging studies in humans have shown that the prefrontal cortex (PFC) is involved in long-term memory functioning. In general, the participation of the PFC in long-term memory has been attributed to its role in executive control rather than information storage. Accumulating data from recent animal studies, however, suggest the possible role of the PFC in the storage of long-term memory. In support of this view, there is evidence that various projection systems in the PFC support long-term synaptic plasticity. Recording studies have further demonstrated neural correlates of learning in various animal species. Lastly, behavioral and physiological studies indicate that the PFC is critically involved in memory consolidation, retrieval and extinction processes. These studies then suggest that the PFC is an integral part of the neural network where long-term memory trace is stored and retrieved. Though decisive evidence is still lacking at present, we propose here to assign a term 'control memory' (i.e., memory for top-down control processes) as a new type of memory function for the PFC. This new principle of PFC-long-term memory can help organize existing data and provide novel insights into future empirical studies.

Encoding of action history in the rat ventral striatum.

In a dynamic environment, animals need to update information about the rewards expected from their alternative actions continually to make optimal choices for its survival. Because the reward resulting from a given action can be substantially delayed, the process of linking a reward to its causative action would be facilitated by memory signals related to the animal's previous actions. Although the ventral striatum has been proposed to play a key role in updating the information about the rewards expected from specific actions, it is not known whether the signals related to previous actions exist in the ventral striatum. In the present study, we recorded neuronal ensemble activity in the rat ventral striatum during a visual discrimination task and investigated whether neuronal activity in the ventral striatum encoded signals related to animal's previous actions. The results show that many neurons modulated their activity according to the animal's goal choice in the previous trial, indicating that memory signals for previous actions are available in the ventral striatum. In contrast, few neurons conveyed signals on impending goal choice of the animal, suggesting the absence of decision signals in the ventral striatum. Memory signals for previous actions might contribute to the process of updating the estimates of rewards expected from alternative actions in the ventral striatum.

Effects of methamphetamine on single unit activity in rat medial prefrontal cortex in vivo.

To investigate how neuronal activity in the prefrontal cortex changes in an animal model of schizophrenia, we recorded single unit activity in the medial prefrontal cortex of urethane-anesthetized and awake rats following methamphetamine (MA) administration. Systemic MA injection (4 mg/kg, IP) induced inconsistent changes, that is, both enhancement and reduction, in unit discharge rate, with a subset of neurons transiently (<30 min) elevating their activities. The direction of firing rate change was poorly predicted by the mean firing rate or the degree of burst firing during the baseline period. Also, simultaneously recorded units showed opposite directions of firing rate change, indicating that recording location is a poor predictor of the direction of firing rate change. These results raise the possibility that systemic MA injection induces random bidirectional changes in prefrontal cortical unit activity, which may underlie some of MA-induced psychotic symptoms.

Role of active movement in place-specific firing of hippocampal neurons.

The extent of external and internal factors contributing to location-specific firing of hippocampal place cells is currently unclear. We investigated the role of active movement in location-specific firing by comparing spatial firing patterns of hippocampal neurons, while rats either ran freely or rode a motorized cart on the same circular track. Most neurons changed their spatial firing patterns across the two navigation conditions ("remapping"), and they were stably maintained across repeated active or passive navigation sessions. These results show that active movement is a critical factor in determining place-specific firing of hippocampal neurons. This could explain why passive displacement is not an effective way of acquiring spatial knowledge for subsequent active navigation in an unfamiliar environment.