A role for neurogenesis in probabilistic reward learning.

Abstract

Rewards are often unreliable and optimal choice requires behavioral flexibility and learning about the probabilistic nature of uncertain rewards. Probabilistic learning occurs over multiple trials, often without conscious knowledge, and is traditionally associated with striatal function. While the hippocampus is classically recognized for its role in memory for individual experiences, recent work indicates that it is also involved in probabilistic forms of learning but little is known about the features that support such learning. We hypothesized that adult neurogenesis may be involved, because adult-born neurons contribute to both learning and reward-related behaviors. To test this, we used an appetitive probabilistic reversal learning task where a correct lever is rewarded with 80% probability and an incorrect lever is rewarded with 20% probability. Behavioral flexibility was assessed by switching correct-incorrect lever identities after 8 consecutive correct choices. Transgenic male rats that lacked adult neurogenesis displayed an initial deficit in discriminating the correct and incorrect levers, but they were not impaired at reversing behavior when the reward contingencies switched. When reward was withheld after a correct lever choice, neurogenesis-deficient rats were more likely to choose the incorrect lever on the subsequent trial. Also, rats with intact neurogenesis were more sensitive to reward at the incorrect lever. Differences were not observed in control transgenic rats that had intact neurogenesis. These results identify a novel role for neurogenesis in learning about uncertain, probabilistic rewards. Altered sensitivity to reward and negative feedback furthermore implicates neurogenesis in cognitive phenotypes associated with mood disorders such as depression.

Prolonged development of long-term potentiation at lateral entorhinal cortex synapses onto adult-born neurons

“…Preferential targeting by the LEC [37,38], and the extended development of LEC-new neuron plasticity reported here, suggests that adult-born neurons may especially facilitate learning about the cues that make each experience unique. Such a function could contribute to learning about, or responding to, discrete objects and cues [79][80][81][82] (but see [83]). Roles for LEC in learning about cue configurations may also underlie new neuron functions in discrimination between similar contexts and places [39,54,84,85].…”

Probabilistic value learning in medial temporal lobe amnesia

“…Adding to this evidence, other human work examining field potentials in the hippocampus shows maximal neural firing in this region when rewards are uncertain (compared to certain), suggesting the hippocampus may be important for computing a reward uncertainty signal (Vanni‐Mercier, Mauguière, Isnard, & Dreher, 2009). Animal studies also implicate the hippocampus in probabilistic value learning, providing additional converging evidence (e.g., Lee, Ghim, Kim, Lee, & Jung, 2012; Seib, Espinueva, Floresco, & Snyder, 2020).…”

“…However, we deliberately avoided the use of conjunctive stimuli, opting instead for simple patterns as cues. A recent study by Seib et al (2020) similarly showed impaired reward‐based probabilistic learning using very simple cues in transgenic mice lacking adult hippocampal neurogenesis. Akin to our study, the demands on pattern separation in that study are not obvious.…”

Dissociable effects of complement C3 and C3aR on survival and morphology of adult born hippocampal neurons, pattern separation, and cognitive flexibility in male mice

“…Key evidence supporting a role for AHN in pattern separation comes from studies in which ablation of neurogenesis resulted in specific impairments in discriminating stimuli with a high degree of spatial similarity or overlap, but not stimuli that are more readily distinguished [10][11][12] . Evidence also supports an important role for AHN in cognitive flexibility and the underlying processes of behavioural inhibition that allows flexible responding in the face of changing contingencies 5 , and elements of cognitive flexibility and behavioural inhibition have been shown to be sensitive to experimental manipulations of AHN [13][14][15][16][17] .…”