Trace classical conditioning impairment after lesion of the lateral part of the goldfish telencephalic pallium suggests a long ancestry of the episodic memory function of the vertebrate hippocampus.

There is an ongoing debate on the evolutionary origin of the episodic memory function of the hippocampus. A widely accepted hypothesis claims that the hippocampus first evolved as a dedicated system for spatial navigation in ancestral vertebrates, being transformed later in phylogeny to support a broader role in episodic memory with the emergence of mammals. On the contrary, an alternative hypothesis holds that the hippocampus of ancestral vertebrates originally encoded both the spatial and temporal dimensions of relational memories since its evolutionary appearance, thus suggesting that the episodic-like memory function of the hippocampus could be the primitive condition in vertebrate forebrain evolution. The present experiment was aimed at scrutinizing these opposing hypotheses by investigating whether the hippocampal pallium of teleost fish, a vertebrate group that shares with mammals a common ancestor that lived about 400 Mya, is, like the hippocampus of mammals, essential to associate time-discontiguous events. Thus, goldfish with lesions in the ventral part of the dorsolateral pallium (Dlv), a telencephalic region considered homologous to the hippocampal pallium of land vertebrates, were trained in trace versus delay eyeblink-like classical conditioning, two learning procedures that differ only in the temporal relationships between the stimuli to be associated in memory. The results showed that hippocampal pallium lesion in goldfish severely impairs trace conditioning, but spares delay conditioning. This finding challenges the idea that navigation preceded relational memory in evolutionary appearance and suggests the possibility that a relational memory function that associates the experienced events in both the spatial and temporal dimensions could be a primitive feature of the hippocampus that pre-existed in the common ancestor of vertebrates.

Goldfish hippocampal pallium is essential to associate temporally discontiguous events.

There is general agreement that the hippocampus of vertebrates, from fish to mammals, is involved in map-like spatial memory. However, in mammals the role of the hippocampus goes beyond the spatial domain as it is also involved in binding the temporally separate events that compose episodic memories. In this regard, the hippocampus of mammals is essential for trace classical conditioning, in which a stimulus-free time gap separates the conditioned stimulus (CS) and the unconditioned stimulus (US), but not for delay conditioning, in which both stimuli coincide in time. Although the involvement of the hippocampus in encoding relational memories based on a temporal frame-work has been extensively studied in mammals, there is scarce evidence about the possible contribution of the hippocampus of non-mammalian vertebrates to the temporal, non-spatial dimension of relational memories. The present work was aimed to determine if the ventral part of the lateral division of the area dorsalis telencephali (Dlv) of goldfish, proposed as homologous to the hippocampus of mammals, is also involved in trace classical conditioning. With this purpose, goldfish with lesions in Dlv, complete telencephalon ablation and sham operation, were trained in delay and trace heart rate classical conditioning. Dlv lesions severely impaired the acquisition of the conditioned response when a stimulus-free time gap was elapsed between the CS and the US (trace conditioning), but not when both stimuli overlapped in time (delay conditioning), revealing that this region, like the hippocampus of mammals, is essential to form the temporal associative memories required by trace conditioning. Present data suggest that the presence of a hippocampal pallium involved in relational, episodic-like memory that preserves both the spatial and the temporal dimensions of past events, could be a primitive feature of the vertebrate brain that has been conserved through evolution.

Relational and procedural memory systems in the goldfish brain revealed by trace and delay eyeblink-like conditioning.

The presence of multiple memory systems supported by different neural substrata has been demonstrated in animal and human studies. In mammals, two variants of eyeblink classical conditioning, differing only in the temporal relationships between the conditioned stimulus (CS) and the unconditioned stimulus (US), have been widely used to study the neural substrata of these different memory systems. Delay conditioning, in which both stimuli coincide in time, depends on a non-relational memory system supported by the cerebellum and associated brainstem circuits. In contrast, trace conditioning, in which a stimulus-free time gap separates the CS and the US, requires a declarative or relational memory system, thus depending on forebrain structures in addition to the cerebellum. The distinction between the explicit or relational and the implicit or procedural memory systems that support trace and delay classical conditioning has been extensively studied in mammals, but studies in other vertebrate groups are relatively scarce. In the present experiment we analyzed the differential involvement of the cerebellum and the telencephalon in delay and trace eyeblink-like classical conditioning in goldfish. The results show that whereas the cerebellum lesion prevented the eyeblink-like conditioning in both procedures, the telencephalon ablation impaired exclusively the acquisition of the trace conditioning. These data showing that comparable neural systems support delay and trace eyeblink conditioning in teleost fish and mammals suggest that these separate memory systems and their neural bases could be a shared ancestral brain feature of the vertebrate lineage.

Spatial learning-related changes in metabolic brain activity contribute to the delimitation of the hippocampal pallium in goldfish.

Comparative neuroanatomical, developmental and functional evidence suggests that the lateral division of the area dorsalis telencephali (Dl) of the teleost fish is homologous to the hippocampus of tetrapods. Nonetheless, some important aspects of the organization of the hippocampal pallium of teleosts are still under discussion and conflicting hypotheses regarding the extension and demarcation of this region have been proposed. Thus, whereas some authors suggest that the entire Dl region, including its dorsal (Dld) and ventral (Dlv) subdivisions, is homologue to the mammalian hippocampus, others claim that only Dlv should be considered as such. To further elucidate this debate, we investigated the role of Dld and Dlv in one of the most unambiguous functions of the hippocampus, spatial learning. We trained goldfish in a spatial constancy task and mapped the activity of Dld, Dlv, and the medial division of the area dorsalis telencephali (Dm) by means of cytochrome oxidase (CO) histochemistry. The results revealed that training goldfish in the spatial constancy task significantly increased the metabolic activity in Dlv, but not in Dld or Dm, suggesting that only Dlv is critically involved in spatial learning and in this regard comparable to the hippocampus. These data provide additional functional support to the hypotheses that consider Dl as a heterogeneous pallial region and propose that Dlv, but not Dld, might be homologous to the hippocampus.