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Behavioral ecologists and economists emphasize that potential costs, as well as rewards, influence decision making. Although neuroscientists assume that frontal areas are central to decision making, the evidence is contradictory and the critical region remains unclear. Here it is shown that frontal lobe contributions to cost-benefit decision making can be understood by positing the existence of two independent systems that make decisions about delay and effort costs. Anterior cingulate cortex lesions affected how much effort rats decided to invest for rewards. Orbitofrontal cortical lesions affected how long rats decided to wait for rewards. The pattern of disruption suggested the deficit could be related to impaired associative learning. Impairments of the two systems may underlie apathetic and impulsive choice patterns in neurological and psychiatric illnesses. Although the existence of two systems is not predicted by economic accounts of decision making, our results suggest that delay and effort may exert distinct influences on decision making.

Perisomatic inhibition provided by a subgroup of GABAergic interneurons plays a critical role in timing the output of pyramidal cells. To test their contribution at the network and the behavioral level, we generated genetically modified mice in which the excitatory drive was selectively reduced either by the knockout of the GluR-D or by conditional ablation of the GluR-A subunit in parvalbumin-positive cells. Comparable cell type-specific reductions of AMPA-mediated currents were obtained. Kainate-induced gamma oscillations exhibited reduced power in hippocampal slices from GluR-D-/- and GluR-A(PVCre-/-) mice. Experimental and modeling data indicated that this alteration could be accounted for by imprecise spike timing of fast-spiking cells (FS) caused by smaller interneuronal EPSPs. GluR-D-/- and GluR-A(PVCre-/-) mice exhibited similar impairments in hippocampus-dependent tasks. These findings directly show the effects of insufficient recruitment of fast-spiking cells at the network and behavioral level and demonstrate the role of this subpopulation for working and episodic-like memory.

Synaptic plasticity dependent on N-methyl-D-aspartate (NMDA) receptors is thought to underlie certain types of learning and memory. In support of this, both hippocampal long-term potentiation and spatial learning in a watermaze are impaired by blocking NMDA receptors with a selective antagonist D(-)-2-amino-5-phosphonovaleric acid (AP5) or by a mutation in one of the receptor subunits. Here we report, however, that the AP5-induced learning deficit can be almost completely prevented if rats are pretrained in a different watermaze before administration of the drug. This is not because of stimulus generalization, and occurs despite learning of the second task remaining hippocampus dependent. An AP5-induced learning deficit is, however, still seen if the animals are pretrained using a non-spatial task. Thus, despite its procedural simplicity, the watermaze may involve multiple cognitive processes with distinct pharmacological properties; although required for some component of spatial learning, NMDA receptors may not be required for encoding the spatial representation of a specific environment.