Summary Neurons in rodent primary visual cortex (V1) relate operantly conditioned stimulus-reward intervals with modulated patterns of spiking output, but little is known about the locus or mechanism of this plasticity. Here we show that cholinergic basal forebrain projections to V1 are necessary for the neural acquisition, but not the expression, of reward timing in the visual cortex of awake, behaving animals. We then mimic reward timing in vitro by pairing white matter stimulation with muscarinic receptor activation at a fixed interval, and show that this protocol results in the prolongation of electrically-evoked spike train durations out to the conditioned interval. Together, these data suggest that (1) V1 possesses the circuitry and plasticity to support reward time prediction learning and (2) the cholinergic system serves as an important reinforcement signal which, in vivo, conveys to the cortex the outcome of behavior.
Humans experiencing hypoxic conditions exhibit multiple signs of cognitive impairment, and high altitude expeditions may be undermined by abrupt degradation in mental performance. Therefore, the development of psychometric tools to quickly and accurately assess cognitive impairment is of great importance in aiding medical decision-making in the field, particularly in situations where symptoms may not be readily recognized. The present study used the Defense Automated Neurobehavioral Assessment (DANA), a ruggedized and portable neurocognitive assessment tool, to examine cognitive function in healthy human volunteers at sea level, immediately after ascending to an elevation over 5000 m, and following 16 days of acclimatization to this high altitude. The DANA battery begins with a simple reaction time test (SRT1) which is followed by a 20-min series of complex cognitive tests and ends with a second test of simple reaction time (SRT2). Tabulating the performance scores from these two tests allows the calculation of an SRT change score (dSRT=SRT1–SRT2) that reflects the potential effect of mental effort spent during the 20-min testing session. We found that dSRT, but not direct SRT in comparison to sea-level baseline performance, is highly sensitive to acute altitude-related performance deficits and the remission of impairment following successful acclimatization. Our results suggest that dSRT is a potentially useful analytical method to enhance the sensitivity of neurocognitive assessment.
SUMMARYWhile the biological analogue of prediction error has been well characterized in the midbrain dopaminergic system, the possibility of other neuromodulatory systems acting as global reinforcers is a topic of much debate. Reward timing, the phenomenon by which single unit responses in primary visual cortex (V1) reflect an operantly learned stimulus-reward interval, offers a tractable preparation to investigate reinforcement learning in vivo: theoretical work suggests that reward timing results from the interaction of stimulus-evoked recurrent network activity and a global reinforcement signal that indicates the time of received reward. We hypothesized that this signal is conveyed by cholinergic neurons arising from the basal forebrain (BF), a strong candidate system that projects globally to most cortical regions, has a known role in plasticity, and is involved in attention and the representation of salience. To test the necessity of such a signal in entraining reward timing in V1, rats were trained on an initial stimulus-reward contingency, received a neurotoxin in V1 that eliminated BF cholinergic terminals, and subsequently trained on a second contingency. We found that extracellular single unit recordings from V1 of lesioned animals, but not saline-infused controls, failed to show shifted neural reports of reward that matched the new contingency. Importantly, neurons of lesioned animals continued to display intervals associated with the initial contingency, arguing that cholinergic input is required to learn, but not to express, reward timing activity.DESCRIPTION We hypothesized that single unit responses in animals lacking BF cholinergic innervation in V1 would show perseverant reward timing activity under a novel cue-reward contingency. To test this, animals were chronically implanted with microelectrode arrays in V1 and trained to lick a fixed number of times to receive reward after right or left eye stimulation. Following the initial training period, either saline or 192-IgGsaporin -a neurotoxin selective for BF cholinergic neurons and their terminals -was infused into the immediate vicinity of the recording site. After a three day recovery period, animals were given a final session under the initial contingency and then trained under a new contingency. Since the reward timing activity of individual neurons is specific to one eye or the other, average firing rates following stimuli to each eye were evaluated with receiver operator characteristic (ROC) analysis. The neural report of reward was defined as the first moment when the area under the ROC curve fell back to chance with 95% confidence. Figure 1 shows example neurons following the contingency change from a control (A) and a lesioned animal (B). While the control unit reports a time that accords well with the new cue-reward interval, the lesioned unit continues to approximate the previous interval (average reward times before/after contingency change: 1.17s/1.79s for control; 1.49s/0.89s for lesioned). Comparing the distributions of reported r...
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