Distinct effects of brief and prolonged adaptation on orientation tuning in primary visual cortex.

Recent stimulus history-adaptation-alters neuronal responses and perception. Previous electrophysiological and perceptual studies suggest that prolonged adaptation strengthens and makes more persistent the effects seen after briefer exposures. However, no systematic comparison has been made between the effects of adaptation lasting hundreds of milliseconds, which might arise during a single fixation, and the more prolonged adaptation typically used in imaging and perceptual studies. Here we determine how 0.4, 4, and 40 s of adaptation alters orientation tuning in primary visual cortex of anesthetized macaque monkeys, and how quickly responses recover after adapter offset. We measured responses to small (1.3°) and large (7.4°) gratings because previous work has shown that adaptation effects can depend on stimulus size. Adaptation with small gratings reduced responsivity and caused tuning to shift away from the adapter. These effects strengthened with more prolonged adaptation. For responses to large gratings, brief and prolonged adaptation produced indistinguishable effects on responsivity but caused opposite shifts in tuning preference. Recovery from adaptation was notably slower after prolonged adaptation, even when this did not induce stronger effects. We show that our results can be explained by an adaptation-induced weakening of surround suppression, the dynamics of this suppression, and differential effects of brief and prolonged adaptation across response epochs. Our findings show that effects do not simply scale with adaptation duration and suggest that distinct strategies exist for adjusting to moment-to-moment fluctuations in input and to more persistent visual stimuli.

Similar adaptation effects in primary visual cortex and area MT of the macaque monkey under matched stimulus conditions.

Recent stimulus history, or adaptation, can alter neuronal response properties. Adaptation effects have been characterized in a number of visually responsive structures, from the retina to higher visual cortex. However, it remains unclear whether adaptation effects across stages of the visual system take a similar form in response to a particular sensory event. This is because studies typically probe a single structure or cortical area, using a stimulus ensemble chosen to provide potent drive to the cells of interest. Here we adopt an alternative approach and compare adaptation effects in primary visual cortex (V1) and area MT using identical stimulus ensembles. Previous work has suggested these areas adjust to recent stimulus drive in distinct ways. We show that this is not the case: adaptation effects in V1 and MT can involve weak or strong loss of responsivity and shifts in neuronal preference toward or away from the adapter, depending on stimulus size and adaptation duration. For a particular stimulus size and adaptation duration, however, effects are similar in nature and magnitude in V1 and MT. We also show that adaptation effects in MT of awake animals depend strongly on stimulus size. Our results suggest that the strategies for adjusting to recent stimulus history depend more strongly on adaptation duration and stimulus size than on the cortical area. Moreover, they indicate that different levels of the visual system adapt similarly to recent sensory experience.

Adaptation improves performance on a visual search task.

Temporal context, or adaptation, profoundly affects visual perception. Despite the strength and prevalence of adaptation effects, their functional role in visual processing remains unclear. The effects of spatial context and their functional role are better understood: these effects highlight features that differ from their surroundings and determine stimulus salience. Similarities in the perceptual and physiological effects of spatial and temporal context raise the possibility that they serve similar functions. We therefore tested the possibility that adaptation can enhance stimulus salience. We measured the effects of prolonged (40 s) adaptation to a counterphase grating on performance in a search task in which targets were defined by an orientation offset relative to a background of distracters. We found that, for targets with small orientation offsets, adaptation reduced reaction times and decreased the number of saccades made to find targets. Our results provide evidence that adaptation may function to highlight features that differ from the temporal context in which they are embedded.

Somatostatin signaling in neuronal cilia is critical for object recognition memory.

Most neurons possess a single, nonmotile cilium that projects out from the cell surface. These microtubule-based organelles are important in brain development and neurogenesis; however, their function in mature neurons is unknown. Cilia express a complement of proteins distinct from other neuronal compartments, one of which is the somatostatin receptor subtype SST(3). We show here that SST(3) is critical for object recognition memory in mice. sst3 knock-out mice are severely impaired in discriminating novel objects, whereas they retain normal memory for object location. Further, systemic injection of an SST(3) antagonist (ACQ090) disrupts recall of familiar objects in wild-type mice. To examine mechanisms of SST(3), we tested synaptic plasticity in CA1 hippocampus. Electrically evoked long-term potentiation (LTP) was normal in sst3 knock-out mice, while adenylyl cyclase/cAMP-mediated LTP was impaired. The SST(3) antagonist also disrupted cAMP-mediated LTP. Basal cAMP levels in hippocampal lysate were reduced in sst3 knock-out mice compared with wild-type mice, while the forskolin-induced increase in cAMP levels was normal. The SST(3) antagonist inhibited forskolin-stimulated cAMP increases, whereas the SST(3) agonist L-796,778 increased basal cAMP levels in hippocampal slices but not hippocampal lysate. Our results show that somatostatin signaling in neuronal cilia is critical for recognition memory and suggest that the cAMP pathway is a conserved signaling motif in cilia. Neuronal cilia therefore represent a novel nonsynaptic compartment crucial for signaling involved in a specific form of synaptic plasticity and in novelty detection.

Oligonucleotide-mediated survival of motor neuron protein expression in CNS improves phenotype in a mouse model of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is caused by homozygous mutation or deletion of the SMN1 gene encoding survival of motor neuron (SMN) protein, resulting in the selective loss of alpha-motor neurons. Humans typically have one or more copies of the SMN2 gene, the coding region of which is nearly identical to SMN1, except that a point mutation causes splicing out of exon 7 and production of a largely nonfunctional SMNDelta7 protein. The development of drugs that mitigate aberrant SMN2 splicing is an attractive therapeutic approach for SMA. A steric block antisense oligonucleotide (AO) has recently been developed that blocked an intronic splice suppressor element, and enhanced SMN2 exon 7 inclusion in SMA patient fibroblasts. Here, we show that periodic intracerebroventricular (ICV) delivery of this AO resulted in increased SMN expression in brain and spinal cord to as much as 50% of the level of healthy littermates. Real-time PCR of SMN2 transcripts confirmed the AO-mediated increase in full-length SMN. The AO-derived increase in SMN expression led to a concomitant improvement in bodyweight throughout the lifespan of the SMA animals. Treatment of SMA mice with AO also provided partial correction of motor deficits, manifest as improved righting response. Injections of a scrambled oligonucleotide had no effect on SMN expression or phenotype in the SMA mice. Our results validate that AOs that abrogate aberrant splicing of SMN2 are promising compounds for treating SMA.

Single unit activity in the rat superior colliculus during reward magnitude task performance.

Long-Evans hooded rats were trained to run an alternation pattern in a t-maze with low reward (1 pellet) in the food cup of one arm and high reward (3 pellets) in the food cup of the other arm. Single units in the intermediate and deep layers of the superior colliculus were recorded using moveable microelectrodes. Most units showed activity that was associated with food retrieval, with a phasic increase in activity either upon the cessation of running or upon the insertion of the snout into the food cup. Some units (16%) showed different activity patterns upon retrieval of the two magnitudes of reward. Although 70% of the units showed either unimodal or multimodal sensory sensitivity, usually in response to tactile stimulation of the snout, this property was not related to activity associated with food retrieval. These data support previous observations that cells in the rat SC exhibit activity related to food retrieval, and indicate that for some of these neurons the coding reflects the characteristics of the reward stimulus.

Adaptation disrupts motion integration in the primate dorsal stream.

Sensory systems adjust continuously to the environment. The effects of recent sensory experience-or adaptation-are typically assayed by recording in a relevant subcortical or cortical network. However, adaptation effects cannot be localized to a single, local network. Adjustments in one circuit or area will alter the input provided to others, with unclear consequences for computations implemented in downstream circuits. Here, we show that prolonged adaptation with drifting gratings, which alters responses in the early visual system, impedes the ability of area MT neurons to integrate motion signals in plaid stimuli. Perceptual experiments reveal a corresponding loss of plaid coherence. A simple computational model shows how the altered representation of motion signals in early cortex can derail integration in MT. Our results suggest that the effects of adaptation cascade through the visual system, derailing the downstream representation of distinct stimulus attributes.