Where Actions Meet Outcomes: Medial Prefrontal Cortex, Central Thalamus, and the Basal Ganglia.

Medial prefrontal cortex (mPFC) interacts with distributed networks that give rise to goal-directed behavior through afferent and efferent connections with multiple thalamic nuclei and recurrent basal ganglia-thalamocortical circuits. Recent studies have revealed individual roles for different thalamic nuclei: mediodorsal (MD) regulation of signaling properties in mPFC neurons, intralaminar control of cortico-basal ganglia networks, ventral medial facilitation of integrative motor function, and hippocampal functions supported by ventral midline and anterior nuclei. Large scale mapping studies have identified functionally distinct cortico-basal ganglia-thalamocortical subnetworks that provide a structural basis for understanding information processing and functional heterogeneity within the basal ganglia. Behavioral analyses comparing functional deficits produced by lesions or inactivation of specific thalamic nuclei or subregions of mPFC or the basal ganglia have elucidated the interdependent roles of these areas in adaptive goal-directed behavior. Electrophysiological recordings of mPFC neurons in rats performing delayed non-matching-to position (DNMTP) and other complex decision making tasks have revealed populations of neurons with activity related to actions and outcomes that underlie these behaviors. These include responses related to motor preparation, instrumental actions, movement, anticipation and delivery of action outcomes, memory delay, and spatial context. Comparison of results for mPFC, MD, and ventral pallidum (VP) suggest critical roles for mPFC in prospective processes that precede actions, MD for reinforcing task-relevant responses in mPFC, and VP for providing feedback about action outcomes. Synthesis of electrophysiological and behavioral results indicates that different networks connecting mPFC with thalamus and the basal ganglia are organized to support distinct functions that allow organisms to act efficiently to obtain intended outcomes.

Central Thalamic-Medial Prefrontal Control of Adaptive Responding in the Rat: Many Players in the Chamber.

The medial prefrontal cortex (mPFC) has robust afferent and efferent connections with multiple nuclei clustered in the central thalamus. These nuclei are elements in large-scale networks linking mPFC with the hippocampus, basal ganglia, amygdala, other cortical areas, and visceral and arousal systems in the brainstem that give rise to adaptive goal-directed behavior. Lesions of the mediodorsal nucleus (MD), the main source of thalamic input to middle layers of PFC, have limited effects on delayed conditional discriminations, like DMTP and DNMTP, that depend on mPFC. Recent evidence suggests that MD sustains and amplifies neuronal responses in mPFC that represent salient task-related information and is important for detecting and encoding contingencies between actions and their consequences. Lesions of rostral intralaminar (rIL) and ventromedial (VM) nuclei produce delay-independent impairments of egocentric DMTP and DNMTP that resemble effects of mPFC lesions on response speed and accuracy: results consistent with projections of rIL to striatum and VM to motor cortices. The ventral midline and anterior thalamic nuclei affect allocentric spatial cognition and memory consistent with their connections to mPFC and hippocampus. The dorsal midline nuclei spare DMTP and DNMTP. They have been implicated in behavioral-state control and response to salient stimuli in associative learning. mPFC functions are served during DNMTP by discrete populations of neurons with responses related to motor preparation, movements, lever press responses, reinforcement anticipation, reinforcement delivery, and memory delay. Population analyses show that different responses are timed so that they effectively tile the temporal interval from when DNMTP trials are initiated until the end. Event-related responses of MD neurons during DNMTP are predominantly related to movement and reinforcement, information important for DNMTP choice. These responses closely mirror the activity of mPFC neurons with similar responses. Pharmacological inactivation of MD and adjacent rIL affects the expression of diverse action- and outcome-related responses of mPFC neurons. Lesions of MD before training are associated with a shift away from movement-related responses in mPFC important for DNMTP choice. These results suggest that MD has short-term effects on the expression of event-related activity in mPFC and long-term effects that tune mPFC neurons to respond to task-specific information.

Central thalamic inactivation impairs the expression of action- and outcome-related responses of medial prefrontal cortex neurons in the rat.

The mediodorsal (MD) and adjacent intralaminar (IL) and midline nuclei provide the main thalamic input to the medial prefrontal cortex (mPFC) and are critical for associative learning and decision-making. MD neurons exhibit activity related to actions and outcomes that mirror responses of mPFC neurons in rats during dynamic delayed non-match to position (dDNMTP), a variation of DNMTP where start location is varied randomly within an open octagonal arena to avoid confounding behavioral events with spatial location. To test whether the thalamus affects the expression of these responses in mPFC, we inhibited the central thalamus unilaterally by microinjecting muscimol at doses and sites found to affect decision-making when applied bilaterally. Unilateral inactivation reduced normalized task-related responses in the ipsilateral mPFC without disrupting behavior needed to characterize event-related neuronal activity. Our results extend earlier findings that focused on delay-related activity by showing that central thalamic inactivation interferes with responses related to actions and outcomes that occur outside the period of memory delay. These findings are consistent with the broad effects of central thalamic lesions on behavioral measures of reinforcement-guided responding. Most (7/8) of the prefrontal response types affected by thalamic inactivation have also been observed in MD during dDNMTP. These results support the hypothesis that MD and IL act as transthalamic gates: monitoring prefrontal activity through corticothalamic inputs; integrating this information with signals from motivational and sensorimotor systems that converge in thalamus; and acting through thalamocortical projections to enhance expression of neuronal responses in the PFC that support adaptive goal-directed behavior.

Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

Prefrontal Neurons Encode Actions and Outcomes in Conjunction with Spatial Location in Rats Performing a Dynamic Delayed Non-Match to Position Task.

To respond adaptively to change organisms must utilize information about recent events and environmental context to select actions that are likely to produce favorable outcomes. We developed a dynamic delayed nonmatching to position task to study the influence of spatial context on event-related activity of medial prefrontal cortex neurons during reinforcement-guided decision-making. We found neurons with responses related to preparation, movement, lever press responses, reinforcement, and memory delays. Combined event-related and video tracking analyses revealed variability in spatial tuning of neurons with similar event-related activity. While all correlated neurons exhibited spatial tuning broadly consistent with relevant task events, for instance reinforcement-related activity concentrated in locations where reinforcement was delivered, some had elevated activity in more specific locations, for instance reinforcement-related activity in one of several locations where reinforcement was delivered. Timing analyses revealed a limited set of distinct response types with activity time-locked to critical behavioral events that represent the temporal organization of dDNMTP trials. Our results suggest that reinforcement-guided decision-making emerges from discrete populations of medial prefrontal neurons that encode information related to planned or ongoing movements and actions and anticipated or actual action-outcomes in conjunction with information about spatial context.

A pathway for spatial memory encoding.

The medial prefrontal cortex has been shown to play a role for rodents in successful completion of tasks that require spatial memory, but the pathways responsible for the transmission of spatial information to the mPFC, and the nature and timing of such information, are unknown. Recently, Spellman, Rigotti, Ahmari, Fusi, Gogos, and Gordon (Nature, 522, 309-314, 2015) addressed these questions in an eloquent and ingenious series of experiments, which we review in the broader context of the neurobiology of spatial memory.

Clark's nutcrackers (Nucifraga columbiana) are sensitive to distance, but not lighting when caching in the presence of a conspecific.

We examined the caching behavior of the Clark's nutcracker (Nucifraga columbiana), a relatively asocial corvid bird, during social and non-social conditions with conspecifics. Past work by Dally et al., (2004, 2005a) has found that the related but more social scrub jay (Aphelocoma californica) caches food in locations that are far away or that are more dimly illuminated when in the presence of an observer. Here, we used procedures comparable to those of Dally's group to examine if the less social nutcracker is also sensitive to these same factors when caching in the presence of a conspecific. We found that nutcrackers cached nuts farther away, but showed no preference for caching in a dimly compared to a brightly illuminated area when in the presence of a conspecific observer. When comparing the measures of cache protection used in the past work with scrub jays the results are consistent with the social organization of these birds; that is, the less social nutcracker engaged in fewer cache protection behaviors than the more social scrub jays, However, we explore other possible explanations for our findings given the wider body of literature on corvid cache protection suggesting that nutcrackers and scrub jays may be more comparable.

Spatial context learning in pigeons (Columba livia).

In a seminal paper in the cognitive sciences, Chun and Jiang (1998) described the contextual cueing paradigm in which they used artificial stimuli and showed that people became faster to locate a target when the background predicted the location of a target compared to when it did not. Here we examined contextual cueing in pigeons for the first time using artificial stimuli and procedures similar to those of Chun and Jiang. In the first test, we had pigeons search for a target among a display of seven distractors; during one condition, the position of the distractors predicted the location of the target, and in the second condition, there was no relationship between the two. In a second test, we presented the pigeons with the predictive displays from Test 1 and a second set of displays that also predicted the location of a target to see if learning about one set of predictive backgrounds disrupted learning about a second set. The pigeons were quick to acquire context-based knowledge and retain that information when faced with additional contexts. The results suggest that contextual cueing can occur for a variety of stimuli in nonhuman animals and that it may be a common mechanism for processing visual information across a wide variety of species.

The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination.

Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task.

An investigation of quantity discrimination in Clark's nutcrackers (Nucifraga columbiana).

We examined quantity discrimination in the Clark's nutcracker (Nucifraga columbiana), a corvid bird with a strong dependence upon caching and recovering nuts. We presented 2 sets of nuts simultaneously, in 21 different conditions, to see if the nutcrackers could choose the larger of the 2 quantities. The nutcrackers displayed a strong ability to discriminate quantities of nuts. Like other animals tested previously, the nutcrackers' performance decreased as the ratio of the 2 quantities approached 1. Interestingly, at constant distances, the nutcrackers did not have more difficulty with contrasts containing larger quantities. Thus, nutcrackers have a fine sensitivity for discriminating between 2 quantities. We review the relevant literature and explore the possibility that nutcrackers, like some other birds, may have developed a keen ability to discriminate quantities. This ability may have developed as an adaptive specialization to cope with their scatter-hoarding ecology, though the evidence for such a conclusion is mixed.

Tests of inferential reasoning by exclusion in Clark's nutcrackers (Nucifraga columbiana).

We examined inferential reasoning by exclusion in the Clark's nutcracker (Nucifraga columbiana) using two-way object-choice procedures. While other social scatter-hoarding corvids appear capable of engaging in inferential reasoning, it remains unclear if the relatively less social nutcracker is able to do so. In an initial experiment, food was hidden in one of two opaque containers. All of the birds immediately selected the baited container when shown only the empty container during testing. We subsequently examined the nutcrackers in two follow-up experiments using a task that may have been less likely to be solved by associative processes. The birds were trained that two distinctive objects were always found hidden in opaque containers that were always positioned at the same two locations. During testing, one of the two objects was found in a transparent "trash bin" and was unavailable. The birds were required to infer that if one of the objects was in the "trash," then the other object should still be available in its hidden location. Five out of six birds were unable to make this inference, suggesting that associative mechanisms likely accounted for our earlier results. However, one bird consistently chose the object that was not seen in the "trash," demonstrating that nutcrackers may have the ability to use inferential reasoning by exclusion to solve inference tasks. The role of scatter hoarding and social organization is discussed as factors in the ability of corvid birds to reason.

Clark's nutcrackers (Nucifraga columbiana) use gestures to identify the location of hidden food.

Heterospecific cues, such as gaze direction and body position, may be an important source of information that an animal can use to infer the location of resources like food. The use of heterospecific cues has been largely investigated using primates, dogs, and other mammals; less is known about whether birds can also use heterospecific gestures. We tested six Clark's nutcrackers in a two-way object-choice task using touch, point, and gaze cues to investigate whether these birds can use human gestures to find food. Most of the birds were able to use a touch gesture during the first trial of testing and were able to learn to use point and gaze (eyes and head alternation) cues after a limited number of trials. This study is the first to test a non-social corvid on the object-choice task. The performance of non-social nutcrackers is similar to that of more social and related corvids, suggesting that species with different evolutionary histories can utilize gestural information.

Pigeons and people select efficient routes when solving a one-way "traveling salesperson" task.

The authors presented people (Experiment 1) and pigeons (Experiments 2 and 3) with a large number of 1-way traveling salesperson problems that consisted of 3, 4, and 5 identical stimuli (nodes) on a computer monitor. The sequence of nodes that each traveler selected was recorded, and the distance of the route was subsequently determined. The routes the pigeons and people selected were reliably more efficient than those used by a Monte Carlo model given the same problems. The pigeons' routes were significantly less efficient than a nearest neighbor model of performance, however. In Experiment 3, pigeons were required to select a route that was within the top 33% of all possible solutions for a given problem. The pigeons' solutions were significantly more efficient than those observed in Experiment 2, in which the behavioral criterion was not imposed. The mechanisms that pigeons and people may have been using to solve the traveling salesperson problems are discussed.

Rats (Rattus norvegicus) encode the shape of an array of discrete objects.

To navigate efficiently, a traveler must establish a heading using a frame of reference. A large body of evidence has indicated that humans and a variety of nonhuman animals utilize the geometry, or shape, of enclosed spaces as a frame of reference to determine their heading. An important and yet unresolved question is whether shape information from arrays of discrete objects and enclosed environments are represented, and utilized, in the same way. In the present study, rats were presented with a reference memory task in which they had to find water that was hidden in 1 of 4 discrete and unique objects placed at the vertices of a rectangle. The results indicate that rats could utilize both feature and geometry cues to locate the hidden goal. The rats' performance declined during transformation tests using a triangular array, indicating that the rats may have encoded the primary axis of the object array, rather than local cues, to direct their search.

Nonaccidental properties underlie shape recognition in Mammalian and nonmammalian vision.

An infinite number of 2D patterns on the retina can correspond to a single 3D object. How do visual systems resolve this ill-posed problem and recognize objects from only a few 2D retinal projections in varied exposure conditions? Theories of object recognition rely on the nonaccidental statistics of edge properties, mainly symmetry, collinearity, curvilinearity, and cotermination. These statistics are determined by the image-formation process (i.e., the 2D retinal projection of a 3D object ); their existence under a range of viewpoints enables viewpoint-invariant recognition. An important question in behavioral biology is whether the visual systems of nonmammalian animals have also evolved biases to utilize nonaccidental statistics . Here, we trained humans and pigeons to recognize four shapes. With the Bubbles technique, we determined which stimulus properties both species used to recognize the shapes. Both humans and pigeons used cotermination, the most diagnostic nonaccidental property of real-world objects, despite evidence from a model computer observer that cotermination was not the most diagnostic pictorial information in this particular task. This result reveals that a nonmammalian visual system that is different anatomically from the human visual system is also biased to recognize objects from nonaccidental statistics.

Applying bubbles to localize features that control pigeons' visual discrimination behavior.

The authors trained pigeons to discriminate images of human faces that displayed: (a) a happy or a neutral expression or (b) a man or a woman. After training the pigeons, the authors used a new procedure called Bubbles to pinpoint the features of the faces that were used to make these discriminations. Bubbles revealed that the features used to discriminate happy from neutral faces were different from those used to discriminate male from female faces. Furthermore, the features that pigeons used to make each of these discriminations overlapped those used by human observers in a companion study (F. Gosselin & P.G. Schyns, 2001). These results show that the Bubbles technique can be effectively applied to nonhuman animals to isolate the functional features of complex visual stimuli.

The fine-grained spatial abilities of three seed-caching corvids.

We used a psychophysical method to examine the ability of three corvid species to discern fine-grained spatial information. Nutcrackers, pinyon jays, and scrub-jays were required to discriminate the distance between two landmarks on a computer screen in an operant chamber. All three species were able to discriminate between arrays that differed by 20 mm; the discrimination gradients for scrub-jays and pinyon jays were sharper than those for nutcrackers, however. The results suggest that differences in spatial memory among these species are not related to differences in fine-grained perception.

Place versus response learning revisited: tests of blocking on the radial maze.

Neurobiological and behavioral research indicates that place learning and response learning occur simultaneously, in parallel. Such findings seem to conflict with theories of associative learning in which different cues compete for learning. The authors conducted place+response training on a radial maze and then tested place learning and response learning separately by reconfiguring the maze in various ways. Consistent with the effects of manipulating place and response systems in the brain (M. G. Packard & J. L. McGaugh, 1996), well-trained rats showed strong place learning and strong response learning. Three experiments using associative blocking paradigms indicated that prior response learning interferes with place learning. Blocking and related tests can be used to better understand how memory systems interact during learning.

Looking for inhibition of return in pigeons.

We conducted four experiments in order to investigate whether pigeons' responses to a recently attended (i.e., recently pecked) location are inhibited. In Experiments 1 and 2, stimulus displays were similar to those used in studies of inhibition of return (IOR) with humans; responses to cued targets tended to be facilitated rather than inhibited. In Experiments 3 and 4, birds were presented with stimulus displays that mimicked clusters of small grains and were relatively localized, which should have been more appropriate for detecting IOR in pigeons. The results from these experiments again provided evidence for facilitation of responding to cued targets, rather than for IOR.

Recent advances in operant conditioning technology: a versatile and affordable computerized touchscreen system.

We report the construction of a new operant chamber that incorporates modern computer, touchscreen, and display technologies. An LCD display was housed in the front wall of a lightweight Plexiglas chamber. An Apple eMac computer was used to present visual stimuli on the monitor and to control other chamber events. Responses to the stimuli were recorded using a transparent resistive-type touchscreen that overlaid the monitor. The resulting system is simple and inexpensive to construct but powerful and flexible enough to explore a broad range of issues in animal learning and behavior.