Faculty Bibliography

The representation of value is a critical component of decision making. Rational choice theory assumes that options are assigned absolute values, independent of the value or existence of other alternatives. However, context-dependent choice behavior in both animals and humans violates this assumption, suggesting that biological decision processes rely on comparative evaluation. Here we show that neurons in the monkey lateral intraparietal cortex encode a relative form of saccadic value, explicitly dependent on the values of the other available alternatives. Analogous to extra-classical receptive field effects in visual cortex, this relative representation incorporates target values outside the response field and is observed in both stimulus-driven activity and baseline firing rates. This context-dependent modulation is precisely described by divisive normalization, indicating that this standard form of sensory gain control may be a general mechanism of cortical computation. Such normalization in decision circuits effectively implements an adaptive gain control for value coding and provides a possible mechanistic basis for behavioral context-dependent violations of rationality.

Standard methods for behavioral and neurophysiological experiments in the non-human primate rely on controlled water access as a means for motivating subject performance. It is, however, still not clear whether animals are able to regulate their fluid balance appropriately under these experimental settings. Further, the physical state associated with a subject monkey's thirst has not yet been objectively assessed under these conditions. Both of these deficiencies arise from the lack of a method for independently evaluating the hydration state of these subjects during experimental testing. To address these limitations, we measured the blood osmolality, the most widely used hematological index of hydration status, of three rhesus monkeys under conditions of controlled water access while they participated in a standard reinforced behavioral task for fluid rewards. We found that day-to-day hydration levels, as measured by serum osmolality, appears to be well regulated in a narrow range of values (300-320 mOsmo/kg H(2)O) by experimental subjects under these conditions: animals work harder and longer to earn more water rewards on a day when they are in a lower hydration state (higher osmolality) than when they are in a higher hydration state (lower osmolality). We also found that osmolality level decreases almost immediately after water intake, within 30 min, in a surprisingly linear manner. Osmolality thus seems to provide a fairly precise reflection of the monkeys' hydration state on a timescale of minutes. This evidence suggests that osmolality can be used as a tool for monitoring the hydration level of experimental subjects.

The mathematical formulations used to study the neurophysiological signals governing choice behavior fall under one of two major theoretical frameworks: "choice probability" or "subjective value." These two formulations represent behavioral quantities closely tied to the decision process, but it is unknown whether one of these variables, or both, dominates the neural mechanisms that mediate choice. Value and choice probability are difficult to distinguish in practice, because higher-valued options are chosen more frequently in free-choice tasks. This distinction is particularly relevant for sensorimotor areas such as parietal cortex, where both value information and motor signals related to choice have been observed. We recorded the activity of neurons in the lateral intraparietal area while monkeys performed an intertemporal choice task for rewards differing in delay to reinforcement. Here we show that the activity of parietal neurons is precisely correlated with the individual-specific discounted value of delayed rewards, with peak subjective value modulation occurring early in task trials. In contrast, late in the decision process these same neurons transition to encode the selected action. When directly compared, the strong delay-related modulation early during decision making is driven by subjective value rather than the monkey's probability of choice. These findings show that in addition to information about gains, parietal cortex also incorporates information about delay into a precise physiological correlate of economic value functions, independent of the probability of choice.

Human dreaming occurs during rapid eye movement (REM) sleep. To investigate the structure of neural activity during REM sleep, we simultaneously recorded the activity of multiple neurons in the rat hippocampus during both sleep and awake behavior. We show that temporally sequenced ensemble firing rate patterns reflecting tens of seconds to minutes of behavioral experience are reproduced during REM episodes at an equivalent timescale. Furthermore, within such REM episodes behavior-dependent modulation of the subcortically driven theta rhythm is also reproduced. These results demonstrate that long temporal sequences of patterned multineuronal activity suggestive of episodic memory traces are reactivated during REM sleep. Such reactivation may be important for memory processing and provides a basis for the electrophysiological examination of the content of dream states.

The retinoblastoma protein (pRb) functions as a regulator of cell proliferation and in turn is regulated by cyclin-dependent kinases. Cyclins D1 and D3 can form complexes with pRb that resemble those formed by several viral oncoproteins and are disrupted by the adenovirus E1A oncoprotein and derived peptides. These cyclins contain a sequence motif similar to the pRb-binding conserved region II motif of the viral oncoproteins. Alteration of this motif in cyclin D1 prevents formation of cyclin D1-pRb complexes while enhancing the biological activity of cyclin D1 assayed in vivo. We conclude that cyclins D1 and D3 interact with pRb in a fashion distinct from cyclins A and E, which can induce pRb hyperphosphorylation, and that cyclin D1 activity may be regulated by its association with pRb.