Subhojit Chakraborty

What does the mediodorsal thalamus do

Dense amnesia can result from damage to the medial diencephalon in humans and in animals. In humans this damage is diffuse and can include the mediodorsal nuclei of the thalamus. In animal models, lesion studies have confirmed the mediodorsal thalamus (MD) has a role in memory and other cognitive tasks, although the extent of deficits is mixed. Anatomical tracing studies confirm at least three different subgroupings of the MD: medial, central, and lateral, each differentially interconnected to the prefrontal cortex (PFC). Moreover, these subgroupings of the MD also receive differing inputs from other brain structures, including the basal ganglia thus the MD subgroupings form key nodes in interconnected frontal-striatal-thalamic neural circuits, integrating critical information within the PFC. We will provide a review of data collected from non-human primates and rodents after selective brain injury to the whole of the MD as well as these subgroupings to highlight the extent of deficits in various cognitive tasks. This research highlights the neural basis of memory and cognitive deficits associated with the subgroupings of the MD and their interconnected neural networks. The evidence shows that the MD plays a critical role in many varied cognitive processes. In addition, the MD is actively processing information and integrating it across these neural circuits for successful cognition. Having established that the MD is critical for memory and cognition, further research is required to understand how the MD specifically influences these cognitive processing carried out by the brain.

Evidence for Mediodorsal Thalamus and Prefrontal Cortex Interactions during Cognition in Macaques.

It is proposed that mediodorsal thalamus contributes to cognition via interactions with prefrontal cortex. However, there is relatively little evidence detailing the interactions between mediodorsal thalamus and prefrontal cortex linked to cognition in primates. This study investigated these interactions during learning, memory, and decision-making tasks in rhesus monkeys using a disconnection lesion approach. Preoperatively, monkeys learned object-in-place scene discriminations embedded within colorful visual backgrounds. Unilateral neurotoxic lesions to magnocellular mediodorsal thalamus (MDmc) impaired the ability to learn new object-in-place scene discriminations. In contrast, unilateral ablations to ventrolateral and orbital prefrontal cortex (PFv+o) left learning intact. A second unilateral MDmc or PFv+o lesion in the contralateral hemisphere to the first operation, causing functional MDmc–PFv+o disconnection across hemispheres, further impaired learning object-in-place scene discriminations, although object discrimination learning remained intact. Adaptive decision-making after reward satiety devaluation was also reduced. These data highlight the functional importance of interactions between MDmc and PFv+o during learning object-in-place scene discriminations and adaptive decision-making but not object discrimination learning. Moreover, learning deficits observed after unilateral removal of MDmc but not PFv+o provide direct behavioral evidence of the MDmc role influencing more widespread regions of the frontal lobes in cognition.

Visual Receptive Field Properties of Neurons in the Mouse Lateral Geniculate Nucleus

The lateral geniculate nucleus (LGN) is increasingly regarded as a “smart-gating” operator for processing visual information. Therefore, characterizing the response properties of LGN neurons will enable us to better understand how neurons encode and transfer visual signals. Efforts have been devoted to study its anatomical and functional features, and recent advances have highlighted the existence in rodents of complex features such as direction/orientation selectivity. However, unlike well-researched higher-order mammals such as primates, the full array of response characteristics vis-à-vis its morphological features have remained relatively unexplored in the mouse LGN. To address the issue, we recorded from mouse LGN neurons using multisite-electrode-arrays (MEAs) and analysed their discharge patterns in relation to their location under a series of visual stimulation paradigms. Several response properties paralleled results from earlier studies in the field and these include centre-surround organization, size of receptive field, spontaneous firing rate and linearity of spatial summation. However, our results also revealed “high-pass” and “low-pass” features in the temporal frequency tuning of some cells, and greater average contrast gain than reported by earlier studies. In addition, a small proportion of cells had direction/orientation selectivity. Both “high-pass” and “low-pass” cells, as well as direction and orientation selective cells, were found only in small numbers, supporting the notion that these properties emerge in the cortex. ON- and OFF-cells showed distinct contrast sensitivity and temporal frequency tuning properties, suggesting parallel projections from the retina. Incorporating a novel histological technique, we created a 3-D LGN volume model explicitly capturing the morphological features of mouse LGN and localising individual cells into anterior/middle/posterior LGN. Based on this categorization, we show that the ON/OFF, DS/OS and linear response properties are not regionally restricted. Our study confirms earlier findings of spatial pattern selectivity in the LGN, and builds on it to demonstrate that relatively elaborate features are computed early in the visual pathway.

Critical role for the mediodorsal thalamus in permitting rapid reward-guided updating in stochastic reward environments

Adaptive decision-making uses information gained when exploring alternative options to decide whether to update the current choice strategy. Magnocellular mediodorsal thalamus (MDmc) supports adaptive decision-making, but its causal contribution is not well understood. Monkeys with excitotoxic MDmc damage were tested on probabilistic three-choice decision-making tasks. They could learn and track the changing values in object-reward associations, but they were severely impaired at updating choices after reversals in reward contingencies or when there were multiple options associated with reward. These deficits were not caused by perseveration or insensitivity to negative feedback though. Instead, monkeys with MDmc lesions exhibited an inability to use reward to promote choice repetition after switching to an alternative option due to a diminished influence of recent past choices and the last outcome to guide future behavior. Together, these data suggest MDmc allows for the rapid discovery and persistence with rewarding options, particularly in uncertain or changing environments. DOI: http://dx.doi.org/10.7554/eLife.13588.001

Demonstration of an eye-movement-induced visual motion illusion (Filehne illusion) in Rhesus monkeys.

During pursuit eye movements, the world around us remains perceptually stable despite the retinal-image slip induced by the eye movement. It is commonly held that this perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. However, if the reference signal is too small or too large, a false eye-movement-induced motion of the external world, the Filehne illusion (FI), will be perceived. A reference signal of inadequate size can be simulated experimentally by asking human subjects to pursue a target across backgrounds with externally added motion that are perceived as moving. In the present study we asked if non-human primates respond to such manipulation in a way comparable to humans. Using psychophysical methods, we demonstrate that Rhesus monkeys do indeed experience a percept of pursuit-induced background motion. In this study we show that an FI can be predictably induced in Rhesus monkeys. The monkey FI shows dependencies on the size and direction of background movement, which is very similar to the ones characterizing the human FI. This congruence suggests that the perception of self-induced visual motion is based on similar inferential mechanisms in non-human and human primates.

Macaque parvocellular mediodorsal thalamus: dissociable contributions to learning and adaptive decision-making

Distributed brain networks govern adaptive decision‐making, new learning and rapid updating of information. However, the functional contribution of the rhesus macaque monkey parvocellular nucleus of the mediodorsal thalamus (MDpc) in these key higher cognitive processes remains unknown. This study investigated the impact of MDpc damage in cognition. Preoperatively, animals were trained on an object‐in‐place scene discrimination task that assesses rapid learning of novel information within each session. Bilateral neurotoxic (NMDA and ibotenic acid) MDpc lesions did not impair new learning unless the monkey had also sustained damage to the magnocellular division of the MD (MDmc). Contralateral unilateral MDpc and MDmc damage also impaired new learning, while selective unilateral MDmc damage produced new learning deficits that eventually resolved with repeated testing. In contrast, during food reward (satiety) devaluation, monkeys with either bilateral MDpc damage or combined MDpc and MDmc damage showed attenuated food reward preferences compared to unoperated control monkeys; the selective unilateral MDmc damage left performance intact. Our preliminary results demonstrate selective dissociable roles for the two adjacent nuclei of the primate MD, namely, MDpc, as part of a frontal cortical network, and the MDmc, as part of a frontal‐temporal cortical network, in learning, memory and the cognitive control of behavioural choices after changes in reward value. Moreover, the functional cognitive deficits produced after differing MD damage show that the different subdivisions of the MD thalamus support distributed neural networks to rapidly and fluidly incorporate task‐relevant information, in order to optimise the animals’ ability to receive rewards.