Neuwelt et al. have proposed gene-transfer experiments utilizing an animal model that offers many important advantages for investigating the feasibility of gene therapy in the human brain. A variety of tissues concerning the viral vector and mode of delivery of the corrective genes need to be resolved, however, before such therapy is scientifically supportable.

The postulated hippocampal comparator, like any other subsystem, must rely on “syntactic” patterns in its “input,” and hence could not have the extraordinary powers Gray supposes. It may play a more modest role, but it is not the place “where it all comes together” for consciousness.

Considerable progress has been made toward understanding the involvement of recoverin in a cancer-associated retinopathy (CAR) that results in blindness. We describe the expression of recoverin in tumors of individuals afflicted with CAR, characterize the immunological response towards recoverin in these patients, and demonstrate how the disease can be induced in rodents using recoverin as an immunogen.

Blocks distinction between “phenomenal feel” consciousness and “thought/cognition” consciousness is a cultural construction. Consciousness (and its “subspecies”) is not a natural kind. Some crosscultural data are presented to support this.

This commentary is divided into two parts. The first considers a possible role for Gray's predictor plus comparator mechanism in human episodic recognition memory. It draws on the computational specifications of recognition outlined in Humphreys et al. (1994) to demonstrate how the logically necessary components of recognition tasks might be mapped onto the mechanism. The second part demonstrates how the mechanism outlined by Gray might be implicated in a form of imitative learning suitable for the acquisition of complex tasks.

Block has attempted to reduce the confusion and controversy concerning the term “consciousness” by suggesting that there are two forms or types of consciousness, each of which has several characteristics or properties. This suggestion appears to further becloud the topic, however. Perhaps consciousness cannot be defined adequately and should not be considered as a topic that can be studied scientifically.

The transition from research to patient following advances in transplantation research is likely to be disappointing unless it includes a better understanding of critically relevant characteristics of the neurological disorder and improvements in the animal models, particularly the behavioral features. The appropriateness of the model has less to do with the species than with how the species is used.

It has been suggested that type I adenylyl cyclase may play a unique role in long-term potentiation, due to both unique regulatory properties as well as a specialized distribution within the mammalian brain. This would allow an integration of the signals wrought by increased intracellular calcium with those conveyed into the cellular milieu via increased cAMP. These results are discussed in the context of changes in cellular structure, because of changing interactions between G proteins and cytoskeletal components, which might be expected to accompany chronic synaptic activation.

Gene replacement therapy holds great promise in the treatment of many genetic CNS disorders. This commentary discusses the feasibility of gene replacement therapy in the unique context of the retina, with regard to: (1) the genetics of retinal neoplasia and degeneration, (2) available gene transfer technology, and (3) potential gene delivery vehicles.

Some cases of prosopagnosia involve a highly circumscribed loss of A-consciousness. When seen in this way they offer further support for the arguments made in Block's target article.

Robust theories concerning the connection between consciousness and brain function should derive not only from empirical evidence but also from a well grounded inind-body ontology. In the case of the comparator hypothesis, Gray develops his ideas relying extensively on empirical evidence, but he bounces irresolutely among logically incompatible metaphysical theses which, in turn, leads him to excessively skeptical conclusions concerning the naturalization of consciousness.

Our results on hippocampal long-term potentiation are considered in the context of Xia et al.'s hypothesis. Whereas the target article proposes presynaptic PKC involvement in adenylyl cyclase activation by phosphorylation of nenromodulin, we suggest an additional postsynaptic role involving RC3/nenrogranin. Finally, we examine the possibility that the adenylyl cyclase mutant mouse may display normal learning with a selective impairment of memory.

We concur that basic research on the use of CNS grafts is needed. Two important model systems for functional studies of grafts are ignored by Stein & Glasier. In the first, reproductive function is restored in hypogonadal mice by transplantation of GnRH-synthesizing neurons. In the second, circadian rhythmicity is restored by transplantation of the suprachiasmatic nucleus.

Gray's account is remarkable in its depth and scope but too little attention is paid to poor correspondences with the literature on hippocampal/subicular damage, the theta rhythm, and novelty detection. An alternative account, focusing on hippocampal involvement in organizing memories in a way that makes them accessible to conscious recollection but not in access to consciousness per se, avoids each of these limitations.

Calcium acting through calmodulin has been shown to regulate the affinity of cyclic nucleotide-gated channels expressed in cell lines. But is calmodulin the Ca-sensor that normally regulates these channels?

In Feeling of Knowing cases, subjects have a form of consciousness about the presence of a content (such as an item of information) without having access to it. If this phenomenon can be correctly interpreted as having to do with consciousness, then there would be a P-conscious mental experience which is dissociated from access.

Amino-terminal heteroacylation has been identified in retinal proteins including recoverin and α subunit of G-protein, transducin. The tissue-specific modification seems to mediate not only a proteinmembrane interaction but also a specific protein-protein interaction. The mechanism generating the heterogeneity and its physiological role are still unclear, but an interesting idea for the latter postulates a fine regulation of the signal transduction pathway by distinct N-acyl groups.

The commentary argues (1) that we cannot be sure that human consciousness has survival value and (2) that in order to understand the origins and, perhaps, the function of consciousness, we should examine the behavioural and neural precursors to consciousness in nonhumans. An example is given of research on the role of context in decisions regarding fleeing from probable predators in the Mongolian gerbil.

The responses displayed by an injured or diseased nervous system are complex. Some of the responses may effect a functional reorganization of the affected neural circuitry. Strategies aimed at the restoration of function, whether or not these involve transplantation, need to recognize the innate reactive capacity of the nervous system to damage. More successful strategies will probably incorporate, rather than ignore, the adaptive responses of the compromised neural systems.