For focal neurodegenerative diseases or brain tumors, localized delivery of protein or genetic vectors may be sufficient to alleviate symptoms, halt disease progression, or even cure the disease. One may circumvent the limitation imposed by the blood-brain barrier by transplantation of genetically altered cell grafts or focal inoculation of virus or protein. However, permanent gene replacement therapy for diseases affecting the entire brain will require global delivery of genetic vectors. The neurotoxicity of currently available viral vectors and the transient nature of transgene expression in vivo must be overcome before their use in human gene therapy becomes clinically applicable.

To explore the mechanism of sensation correlations between EP (evoked potential) component amplitude and signal detection indices (d' and criterion) were studied. The time of sensation coincided with the peak latency of those EP components that showed a correlation with both indices. The components presumably reflected information synthesis in projection cortical neurons. A mechanism providing the synthesis process is proposed.

Many now consider “instinct” and “learning” opposite poles of a unidimensional continuum. An alternative model with two independently varying parameters predicts different selective pressures. Behavioral adaptation matches the organism's utilizations of stimuli and responses to their ecological validities: the mean validity over evolutionary time specifies the optimal initial potency of the prepared association; the variance specifies the optimal prepared plasticity.

Our understanding of the molecular properties and cellular role of cGMP-gated channels in outer segments of vertebrate photo-receptors has come from over a decade of studies which have continuously altered and refined ideas about these channels. Further examination of this current view may lead to future surprises and further refine the understanding of cGMP-gated channels.

The use of neural transplantation to alleviate cognitive deficits is still in its infancy. We have an inadequate understanding of the deficits induced by different types of brain damage and their homologies in animal models against which to assess graft-induced recovery, and of the ways in which graft growth and function are influenced by factors within the host brain and the environment in which the host is operating. Further, use of fetal tissue may only be a transitory phase in the search for appropriate donor sources. Nevertheless, findings from our laboratory and elsewhere have made a prima facie case for successful cognitive reconstruction by graft methods.

As Gray insists, his comparator model proposes a brute correlation only – of consciousness with septohippocampal output. I suggest that the comparator straddles a feedback loop that boosts the activation of novel representations, thus helping them feature in present or recollected experience. Such a role in organizing conscious contents would transcend correlation and help explain how consciousness emerges from brain function.

The present commentary emphasizes that the acquisition of fear always involves complex changes in several quasi-independent response systems. Stimulus-specific electrodermal response differentiation as well as the bias to overestimate the belongingness of certain stimulus pairs mainly indicates cognitive processes of selective orienting and attention. Emotion, however, also involves the activation of subcortical motivational circuits. Why certain stimuli acquire rapid access to these basic motivational systems is not explained by the expectancy bias model.

Cyclic nucleotides can regulate the sensitivity of retinal rods to light through phosducin. The phosphorylation state of phosducin determines the amount of G available for activation by Rho*. Phosducin phosphorylation is regulated by cyclic nucleotides through their activation of cAMP-dependent protein kinase. The regulation of phosphodiesterase activity by the noncatalytic cGMP binding sites as well as Ca2+/calmodulin dependent regulation of cGMP binding to the cation channel are also discussed.

Gray's integration of the different levels of description and explanation in his theory is problematic: (1) The introduction of consciousness into his theorising consists of the mind-brain identity assumption, which tells us nothing new. (2) There need not be correlations between levels of description. (3) Gray's account does not extend beyond “brute” correlation. Integration must be achieved in a principled, mutually constraining way.

In the current model of visual transduction, the lifetime of active cGMP phosphodiesterase depends upon the period of its interaction with GTP-bound transducin. If recoverin regulates the lifetime of light-activated cGMP phosphodiesterase through inhibition of rhodopsin phosphorylation, rhodopsin should directly interact with cGMP phosphodiesterase and/or GTP-bound transducin complexed with cGMP phosphodiesterase. Is this true?

Despite some clinical promise, using fetal transplants for degenerative and traumatic brain injury remains controversial and a number of issues need further attention. This response reexamines a number of questions. Issues addressed include: temporal factors relating to neural grafting, the role of behavioral experience in graft outcome, and the relationship of rebuilding of neural circuitry to functional recovery. Also discussed are organization and type of transplanted tissue, the “trophic hypothesis” of transplant viability, and whether transplants are really needed to obtain functional recovery after brain damage.

Davey's discussion of phobias is criticized because of the lack of distinctions between the various classes of phobias. Psychopharmacological evidence indicates differing pathophysiologies. Clinical psychopharmacological distinctions are not congruent with either a strict phylogenetic preparedness model or with cognitive biases. Davey's critique of the laboratory bred animal studies seems far fetched. His hypothesis concerning the importance of historical significance is clearly ad hoc rather than based on comparative data.

To avoid teleological interpretations, it is important to make a distinction between functions and uses of consciousness, and to address questions concerning the consequences of consciousness. Assumptions about the phylogenetic distribution of consciousness are examined. It is concluded that there is some value in identifying consciousness an exclusively human attribute.

NMR (nuclear magnetic resonance) may be useful for determining the structure of retinal and its environment in rhodopsin, but not for determining the complete protein structure. Aggregation and low yield of fragments of rhodopsin may make them difficult to study by NMR. A long-term multidisciplinary attack on rhodopsin structure is required.

We endorse Davey's view that expectancy processes are intimately involved in fear reactions, but question his model on three grounds. First, the mechanism for generating expectancy bias to both ontogenetic and phylogenetic stimuli is not spelled out. Second, the selective association component is unnecessary. Third, the model fails to provide a clear explanation for the irrationality of phobic reactions.

Self-control, so important in the theory and practice of psychology, has usually been understood introspectively. This target article adopts a behavioral view of the self (as an abstract class of behavioral actions) and of self-control (as an abstract behavioral pattern dominating a particular act) according to which the development of self-control is a molar/molecular conflict in the development of behavioral patterns. This subsumes the more typical view of self-control as a now/later conflict in which an act of self-control is a choice of a larger but later reinforcer over a smaller but sooner reinforcer. If at some future time the smaller-sooner reinforcer will be more valuable than the larger-later reinforcer, self-control may be achieved through a commitment to the largerlater reinforcer prior to that point. According to some, there is a progressive internalization of commitment in the development of self-control. This presents theoretical and empirical problems. In two experiments – one with pigeons choosing between smallersooner and larger-later reinforcers, the other with adult humans choosing between short-term particular and long-term abstract reinforcers – temporal patterning of choices increased self-control.

The comparator model is insufficient for three reasons. First, consciousness is involved in the process of comparison as well as in the output. Second, we still do not have enough neurophysiological information to match the events of consciousness, although such knowledge is growing. Third, the anatomical localisation proposed can be damaged bilaterally but consciousness will persist.

Contrary to his own perspective, Rachlin introduces a ghostly inner cost to explain the persistence of behavioral patterns and agency to explain their origins. Both inconsistencies can be set straight by taking account of history and a context larger than the pattern itself. Persistence is explained by stimulus control, if one assumes that defection from a pattern has stimulus properties and is punished. The origins of patterns are understood as an outcome of selection in the larger context of cultural or biological evolution.

The generally positive response to our target article indicates that most of the commentators accept our contention that light adaptation consists of multiple and possibly redundant mechanisms. The commentaries fall into three general categories. The first deals with putative mechanisms that we chose not to emphasize. The second is a more extended discussion of the role of calcium in adaptation. Finally, additional aspects of cGMP involvement in adaptation are considered. We discuss each of these points in turn.

In his critique of preparedness theory, Davey does not address the limitations of adaptationism. The purpose of this commentary is to outline problems that arise when one assumes that mental illness (e.g., phobic disorder) must have had adaptive significance for it to have survived the vicissitudes of natural selection.